Relationships of serum haptoglobin concentration with HbA1c and glycated albumin concentrations in Japanese type 2 diabetic patients.
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.
Suzuki
Kaoru
K
Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa City, Japan.
Yagi
Kunimasa
K
Oka
Rie
R
Saiki
Yuko
Y
Kubota
Miyuki
M
Sugihara
Masako
M
Ito
Naoko
N
Kawashiri
Masa-aki
MA
Nohara
Atsushi
A
Horita
Hiroshi
H
Takeda
Yoshiyu
Y
Yamagishi
Masakazu
M
Kobayashi
Junji
J
D000367:Age Factors; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005783:Gender Identity; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis*; D017127:Glycation End Products, Advanced; D006242:Haptoglobins / Q000032:analysis*; D006801:Humans; D007564:Japan; D012709:Serum Albumin / Q000032:analysis*; D000093423:Glycated Serum Albumin
D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006242:Haptoglobins; D012709:Serum Albumin; D000093423:Glycated Serum Albumin