Relationships of serum haptoglobin concentration with HbA_1c and glycated albumin concentrations in Japanese type 2 diabetic patients

Abstract

Background: The stable fractions of glycated hemoglobin (Hb), particularly HbA_1c, and glycated albumin (GA) were measured to monitor chronic glycemic control. Haptoglobin (Hp) is a Hb-binding protein, which plays a major role in preventing free Hb-induced tissue oxidative damage. The aim of this study was to clarify the relationships of serum Hp concentration with HbA_1c and GA concentrations.

Methods: A cross-sectional study to determine the relationship of serum Hp concentration with GA and HbA_1c concentrations was conducted. The subjects were 125 Japanese type 2 diabetic patients with stable HbA_1c levels for more than 3 consecutive months. Patients with altered albumin and red blood cell turnover, which are observed in those with chronic renal failure, liver cirrhosis, and anemia among others, were excluded from the study.

Results: Serum Hp concentration positively correlated with HbA_1c concentration (r=0.30, p<0.001), but not with GA concentration (r=0.15, p=0.10). There was a weak inverse correlation between serum Hp concentration and GA/HbA_1c ratio (r=−0.19, p=0.03). Moreover, GA /HbA_1c ratio inversely correlated with body mass index (BMI) (r=−0.31, p<0.001). In contrast, there was no significant correlation between Hb concentration and HbA_1c (r=0.01, p=0.88) or GA (r=0.12, p=0.21) concentrations. We also analyzed the correlation of serum Hp concentration with GA and HbA_1c concentrations in patients with the Hp 2-1 and Hp 2-2 genotypes, separately. Hp concentration positively correlated with HbA_1c concentration in patients with the Hp 2-1 (r=0.32, p=0.03) and Hp 2-2 (r=0.29, p=0.02) phenotypes. Multiple regression analysis revealed that the observed correlation between Hp and HbA_1c concentrations was significant after adjustment for age, gender, and BMI. In contrast, there was no significant correlation between GA and Hp concentrations in patients with either phenotype. Then, we analyzed how Hp concentration affects GA/HbA_1c ratio in patients with these Hp phenotypes. There was an inverse correlation between Hp concentration and GA/HbA_1c ratio in patients with Hp 2-1 (r=−0.44, p=0.003), but not in those with Hp 2-2 (r=−0.03, p=0.75). Multiple regression analysis revealed that the inverse correlation between Hp concentration and GA/HbA_1c ratio in patients with Hp 2-1 was independent of age, gender, and BMI.

Conclusions: Hp phenotype and concentration should be considered in interpreting HbA_1c and GA levels as glycemic control indicators in diabetic patients. We suggest that in type 2 diabetic patients with Hp 2-1 and high Hp concentrations, HbA_1c level may be overestimated relative to GA level.

Clin Chem Lab Med 2009;47:70–4.