Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Association of Glycated Albumin/Glycosylated Hemoglobin Ratio with Blood Glucose Fluctuation and Long-Term Blood Glucose Control in Patients with Type 2 Diabetes Mellitus Bai-Rong Wang1,2 Objective: This study aimed to investigate the association of the glycated albumin (GA)/ Jun-Teng Yao2 glycosylated hemoglobin (HbA1c) ratio with the mean amplitude of glycemic excursion Hui Zheng1 (MAGE) in type 2 diabetes mellitus (T2DM). Quan-Min Li1 Methods: A total of 102 patients with T2DM who were first treated in Jinjiang Hospital of Fujian Province were enrolled in this study. The patients’ general clinical data, including 1 Department of Endocrinology, Medical HbA1c, GA, fasting blood glucose, and fasting and peak C-peptide values upon diagnosis College of Soochow University, Suzhou 215123, Jiangsu, People's Republic of and after one year of follow-up, were collected, and their MAGE was calculated. China; PLA Rocket Force Characteristic Results: With the increase of the GA/HbA1c ratio at baseline, the patients’ fasting and peak Medical Center, Beijing, 100088, People’s Republic of China; 2Department of C-peptide values decreased gradually from baseline to follow-up, while their MAGE, Endocrinology, Jinjiang Municipal HbA1c, and fasting blood glucose increased gradually. A regression analysis demonstrated Hospital, Jinjiang, 362200, People’s that the baseline MAGE was independently positively correlated with the GA/HbA1c ratio. Republic of China A Cox regression analysis demonstrated that a baseline GA/HbA1c ratio of >2.78 was an independent risk factor for poor fasting blood glucose and HbA1c. Conclusion: The GA/HbA1c ratio is closely related to the MAGE and islet function in patients with T2DM. Keywords: type 2 diabetes mellitus, glycated albumin, glycosylated hemoglobin, blood glucose control, blood glucose fluctuation Introduction Diabetes mellitus is a common disease endangering human health.1 Accumulating evidence shows that blood glucose fluctuation can induce oxidative stress, cause vascular endothelial dysfunction, promote arteriosclerosis, and is associated with the risk of vascular complications in diabetes.2–4 The mean amplitude of glycemic excur­ sion (MAGE) helps accurately evaluate patients’ blood glucose fluctuationbut requires continuous glucose monitoring (CGM) and complicated calculations. In addition, numerous studies have been conducted to examine the relationship between insulin secretion and glucose fluctuation in patients with diabetes.5–7 Jin et al have suggested Correspondence: Quan-Min Li that fasting C-peptide levels are inversely associated with higher glucose fluctuation.6 PLA Rocket Force Characteristic Medical Center, Beijing, 100088, People’s Republic Ohara et al have found increments of C-peptide immunoreactivity correlated with of China glycemic control stability.5 However, it remains unclear which clinical markers are Tel +86 10 66927601 Email [email protected] independently correlated with patients’ blood glucose fluctuation. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2021:14 1809–1815 1809 © 2021 Wang et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Wang et al Dovepress Glycosylated hemoglobin (HbA1c) and glycated albu­ subjects’ informed consent was obtained. This study was min (GA) can be used to evaluate the recent mean blood conducted in accordance with the Declaration of Helsinki. glucose level of diabetic patients, but they cannot reflect the patients’ blood glucose fluctuation. A previous study Methods suggests that decline of islet function is the direct cause of (1) The patients’ clinical data, including age, gender, the increase in blood glucose fluctuation in patients with weight, and height, were collected, and their body mass diabetes.8 The blood glucose fluctuation of type 1 diabetes index (BMI) was calculated. Then, blood was drawn from mellitus (T1DM) can be reflected by the GA/HbA1c ratio, the patients after eight hours of fasting; the maximum which is more convenient than the MAGE.9 The islet delivery time to the laboratory was 30 min. The blood to function of patients with type 2 diabetes mellitus detect blood glucose, alanine aminotransferase (ALT), (T2DM) also decreases progressively. A previous study creatinine, and GA were put in coagulation tubes and has revealed that the GA/HbA1c ratio in patients with measured by a Beckman automatic biochemical analyzer low C-peptide levels is significantly higher than that in (Beckman Coulter lnc, CA, USA) after centrifugation at patients with high C-peptide levels, even after two years of 4,000 rpm for five minutes. The blood to detect HbA1c treatment and follow-up.10 This study suggests that the was put in EDTA-K2 anticoagulant tubes and measured by GA/HbA1c ratio may be a predictor of long-term glycemic a Tosoh G8 detector (Tosoh Bioscience, Tokyo, Japan). To control in patients with T2DM. detect the C-peptide levels, blood was collected in EDTA- To determine the correlation of the GA/HbA1c ratio K2 anticoagulant tubes at one, two, and three hours after with blood glucose fluctuation and long-term blood glu­ oral administration of 75 g of glucose, with the highest cose control in patients with T2DM, the clinical data of level taken as the C-peptide peak. The C-peptide levels 102 patients newly diagnosed with T2DM are collected in were measured by Roche E601 automatic immunoassay this research. This study also aims to determine whether (Roche Diagnostics, Munich, Germany) after centrifuga­ the GA/HbA1c ratio is closely related to the C-peptide tion at 4,000 rpm for five minutes. level and the blood glucose fluctuation range and further (2) After two weeks of treatment, the patients were analyze the correlation of the baseline GA/HbA1c ratio reminded to monitor their blood glucose levels and trans­ with fasting blood glucose (FBG) and HbA1c after mit the monitored values through the app or by phone to one year of follow-up. Finally, it explores the predictive Jinjiang Hospital. For hospitalized patients, the blood glu­ value of the GA/HbA1c ratio for long-term glycemic con­ cose was monitored one week after subcutaneous insulin trol in patients with T2DM. injections. The fingertip blood glucose of outpatients and inpatients was monitored seven times a day for three consecutive days (ACCU-Chek blood glucose meter, Subjects and Methods Roche Diagnosis), including before meals, two hours Subjects after meals, and before going to bed. During the monitor­ The clinical data of 102 patients newly diagnosed with ing period, the treatment plan and hypoglycemia dose T2DM from 2018 to 2019 at the Department of were unchanged. On this basis, the MAGE was calculated. Endocrinology, Jinjiang Hospital, Fujian Province, were The calculation formula was MAGE = ∑λ/χ, where λ is the collected. All patients included met the diagnostic criteria difference between the maximum and minimum values of formulated by the World Health Organization in 1999.11 each effective blood glucose fluctuation and χ is the num­ The exclusion criteria were as follows: (1) kidney insuffi­ ber of effective fluctuations. When the difference between ciency, (2) nephrotic syndrome, (3) liver insufficiency, (4) the peak and trough of a blood glucose fluctuation was anemia, (5) hypoproteinemia, (6) pregnancy, (7) serious greater than one standard deviation of blood glucose, it chronic complications of diabetes mellitus, (8) acute car­ was considered the effective amplitude of blood glucose diovascular and cerebrovascular diseases, and (9) a history fluctuation. of taking glucocorticoids, pentamidine, nicotinic acid, (3) After one year of follow-up, FBG, HbA1c, and GA thyroid hormone, diazoxide, β-adrenergic agonists, thia­ were detected, the islet function was evaluated, a 75-g zide diuretics, Dilantin, interferon-γ, and other drugs that glucose tolerance test was conducted, and the C-peptide affect the blood glucose levels. This study was approved levels at one, two, and three hours after glucose load were by the ethics committee of Jinjiang Hospital, and the detected, with the highest level taken as the peak 1810 http://doi.org/10.2147/DMSO.S297730 Diabetes, Metabolic Syndr ome and Obesity: T argets and Therapy 2021:14 DovePress Dovepress Wang et al C-peptide value. The methods were the same as those Table 1 Comparison of Clinical Indicators Between Baseline and described above. Follow-Up Baseline After Follow- P value Statistical Analysis Up The patients were divided into three groups according to HbA1c (%) 10.31±2.85 7.09±0.89 <0.001 the baseline GA/HbA1c level: <2.62 in group T1, between GA (%) 29.66±11.12 20.33±5.25 <0.001 2.62 and 3.03 in group T2, and >3.03 in group T3. The normally distributed measurement data were expressed as GA/HbA1c ratios 2.84±0.51 2.59±0.61 <0.001 the mean ± standard deviation (x̄ ± SD), compared The fasting C-peptide 1.53±0.75 1.64±0.56 0.115 between two groups using paired t-tests, and compared (ng/mL) among all groups using general linear models. The non- The peak value of 3.05±1.64 3.62±1.37 <0.001 normally distributed measurement data were expressed as C-peptide (ng/mL) the median (range) and compared among the groups using general linear models. These data were included in the analysis after log conversion.