Elsevier

Metabolism

Volume 103, February 2020, 153995
Metabolism

Clinical Science
Clinical usefulness of human serum nonmercaptalbumin to mercaptalbumin ratio as a biomarker for diabetic complications and disability in activities of daily living in elderly patients with diabetes

https://doi.org/10.1016/j.metabol.2019.153995Get rights and content

Highlights

  • Oxidative stress may play an important role in diabetic complications.

  • The ratio of nonmercaptalbumin (HNA%) may be an indicator for systemic redox states.

  • HNA% was associated with vascular complications in elderly patients with diabetes.

  • HNA% was associated with ADL disability in elderly patients with diabetes.

  • HNA% may be a useful oxidative stress biomarker in elderly patients with diabetes.

Abstract

Background

Oxidative stress may play an important role in the development of diabetic complications. The ratio of human nonmercaptalbumin (HNA; oxidized form) to human mercaptalbumin (HMA; reduced form) has attracted attention as an indicator for systemic redox states. In this study, we measured the ratio in elderly patients with diabetes and evaluated its association with diabetic complications and disability in activities of daily living (ADL disability).

Methods

One hundred twenty-six elderly patients with diabetes, aged 70 years and older, under medical care at Yukuhashi Central Hospital from April 2018 to June 2018, were continuously recruited. HNA%, defined as HNA / (HNA + HMA) × 100, was measured by a high-performance liquid chromatography method. First, multivariate regression analysis was performed to evaluate which variables were significant determinants for HNA%. Next, to evaluate the association of HNA% with ADL disability, logistic regression analysis in various models was performed. Then we plotted the receiver operating characteristic (ROC) curve and calculated the under area the curve (AUC), sensitivity, and specificity in each model.

Results

In elderly patients with diabetes, multiple regression analysis showed that serum bilirubin levels and albumin levels, both of which are major endogenous anti-oxidants, and chronic renal failure (or proliferative nephropathy) were significantly associated with HNA%, suggesting that HNA% may be a good biomarker for oxidative stress in those patients. We then evaluated the association of HNA% with ADL disability in various logistic regression models. Model using only HNA% showed that it was a significant determinant for ADL disability (OR 1.158, 95% CI 1.077–1.244, P < 0.001). Model using HNA% and age showed that both variables were significant determinants for ADL disability (OR 1.160, 95% CI 1.069–1.258, P < 0.001; OR 1.258, 95% CI 1.110–1.427, P < 0.001, respectively). ROC analysis showed that the AUC of HNA% alone was 0.765. The AUC of model using HNA% and age was further increased to 0.866.

Conclusions

HNA% was significantly associated with diabetic complications and ADL disability, thereby may be clinically useful as an oxidative stress marker in elderly patients with diabetes.

Introduction

Recent evidence has shown that diabetes is closely associated with frailty and ADL disability as well as vascular complications [1]. Although the mechanism underlying diabetic complications is not fully understood, increasing attention has been paid to oxidative stress. Thus, a sensitive and useful biomarker for evaluating oxidative stress is needed in the clinical setting. Human serum albumin (HSA) is the most abundant protein in blood. HSA contains 35 cysteine residues in its molecule, but only cysteine-34 (Cys34) exists in the free state. HSA is capable of scavenging radicals with this highly reactive reduced Cys34 residue [2]. As a result, HSA exists in two different forms, human mercaptalbumin (HMA; reduced form) and human nonmercaptalbumin (HNA; oxidized form) [3,4]. Thus, the ratio of HNA to HMA may be a good biomarker for systemic oxidative stress [5,6]. Recently, we developed a novel method to measure HNA and HMA using an anion-exchange high performance liquid chromatography (HPLC) system, which are a more rapid, accurate, and reproducible than previous methods [[7], [8], [9]].

In this study, we first examined the association between the ratio of HNA to (HMA + HNA) and oxidative stress-related variables including vascular complications in elderly patients with diabetes. Then, we examined whether this ratio is a significant determinant for ADL disability.

Section snippets

Subjects

In this study, 126 elderly patients with diabetes aged 70 years and older who were under medical care at Yukuhashi Central Hospital were continuously recruited from April 2018 to June 2018. The elderly patients with diabetes were classified into 2 groups: those with ADL disability (n = 20) and those without ADL disability (n = 106). ADL was evaluated by self-report regarding physical ability in basic self-care tasks: mobility, bathing, dressing, eating, and using the toilet. ADL disability was

Results

Characteristics of the 126 elderly patients with diabetes enrolled in our study are shown in Table 1. HNA% was positively correlated with age, and negatively correlated with bilirubin levels, albumin levels, and HbA1c (Supplement Fig. 1). It was significantly higher in patients with hypertension than those without it (Supplement Fig. 2). As stage progressed, HNA% tended to increase in both retinopathy and nephropathy (P < 0.001 for Trends, for both), and HNA% in patients with both proliferative

Discussion

The increase in the oxidized form has been reported in several oxidative stress-related conditions such as renal dysfunction [10], hemodialysis [11], aging [12], and diabetes mellitus [13], although the sample sizes of these studies were very small. The current study showed that serum bilirubin levels, serum albumin levels, and chronic renal failure (or proliferative retinopathy) were significant determinants for HNA% in elderly patients with diabetes. Bilirubin is a strong endogenous

Author contribution

S.F. and T.I. contributed to the concept and design of the study, data acquisition, analysis and interpretation, and writing the manuscript. K.Y., M.S., H.I. and Y.Y. contributed to measurement of non-mercaptalbumin and mercaptalbumin. Y.I., T.E., M.M., S.S., F.U. and T.Y. contributed to data acquisition and interpretation.

Funding

This research did not receive specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors have no potential conflicts of interest to report.

Acknowledgements

We thank nurses at Yukuhashi Central Hospital for assistance with the acquisition of detailed data regarding patients' physical abilities in basic self-care tasks.

References (20)

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