Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verification

AimsTo determine the effect of red blood cell (RBC) lifespan variability on glycosylated hemoglobin (HbA1c) measurements in type 2 diabetes mellitus (T2DM) individuals and develop a mathematical model for adjusting HbA1c values.MethodsWe tracked glucose levels in 516 T2DM patients from Chu Hsien-I M...

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Main Authors: Li Zhang, Ximan Gao, Xuying Meng, Guangyang Ma, Jing Li, Weilin Wang, Sisi Chen, Yongjian Ma, Pei Yu, Saijun Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1500660/full
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author Li Zhang
Li Zhang
Ximan Gao
Ximan Gao
Xuying Meng
Xuying Meng
Guangyang Ma
Guangyang Ma
Jing Li
Jing Li
Weilin Wang
Weilin Wang
Sisi Chen
Sisi Chen
Yongjian Ma
Pei Yu
Pei Yu
Saijun Zhou
Saijun Zhou
author_facet Li Zhang
Li Zhang
Ximan Gao
Ximan Gao
Xuying Meng
Xuying Meng
Guangyang Ma
Guangyang Ma
Jing Li
Jing Li
Weilin Wang
Weilin Wang
Sisi Chen
Sisi Chen
Yongjian Ma
Pei Yu
Pei Yu
Saijun Zhou
Saijun Zhou
author_sort Li Zhang
collection DOAJ
description AimsTo determine the effect of red blood cell (RBC) lifespan variability on glycosylated hemoglobin (HbA1c) measurements in type 2 diabetes mellitus (T2DM) individuals and develop a mathematical model for adjusting HbA1c values.MethodsWe tracked glucose levels in 516 T2DM patients from Chu Hsien-I Memorial Hospital, categorized into Construction (n = 416) and Internal (n = 100) cohorts. Additionally, 165 participants from Tianjin diabetic retinopathy screening cohort, serving as the Independent cohort. RBC lifespan was determined using the CO breath test, and Hemoglobin glycation variation index (HGI) was calculated from the difference between measured and estimated HbA1c (eHbA1c). Model efficacy was evaluated using AUC, accuracy, sensitivity, and specificity.ResultsAn inflection in the HGI-RBC lifespan model occurred at 66 days, with HbA1c underestimation when RBC lifespan was below 90 days, notably in the ≤ 66 days group. This underestimation increased the risk of cardiovascular and peripheral neuropathy complications. To rectify the impact of the shorter RBC lifespan in T2DM patients, the correction formula was established as HbA1c(c) = -0.05629×RBC lifespan + 1.127×HbA1c + 3.178 (R = 0.7360) in the ≤ 66 day lifespan group and HbA1c(c) = -0.004772 × RBC lifespan + 0.7569 × HbA1c + 2.394 (R = 0.7344) in the 67 to 89 day group. The corrected HbA1c models exhibited satisfactory predictive performance in all cohorts.ConclusionsAccurate adjustment for the effects of RBC lifespan on HbA1c values in T2DM patients is expected to enhance blood glucose management and the efficacious prevention and treatment of diabetes-associated complications.Clinical Trial RegistrationChu Hsien-I Memorial Hospital of Tianjin Medical University, identifier ChiCTR2100046557.
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spelling doaj-art-0bee2b3ba0694de09f4f5c1a0b21d11e2025-08-20T02:12:15ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-04-011610.3389/fendo.2025.15006601500660Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verificationLi Zhang0Li Zhang1Ximan Gao2Ximan Gao3Xuying Meng4Xuying Meng5Guangyang Ma6Guangyang Ma7Jing Li8Jing Li9Weilin Wang10Weilin Wang11Sisi Chen12Sisi Chen13Yongjian Ma14Pei Yu15Pei Yu16Saijun Zhou17Saijun Zhou18NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaDepartment of Endocrinology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaGuangdong Breath Test Engineering and Technology Research Center, Shenzhen University, Shenzhen, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, ChinaAimsTo determine the effect of red blood cell (RBC) lifespan variability on glycosylated hemoglobin (HbA1c) measurements in type 2 diabetes mellitus (T2DM) individuals and develop a mathematical model for adjusting HbA1c values.MethodsWe tracked glucose levels in 516 T2DM patients from Chu Hsien-I Memorial Hospital, categorized into Construction (n = 416) and Internal (n = 100) cohorts. Additionally, 165 participants from Tianjin diabetic retinopathy screening cohort, serving as the Independent cohort. RBC lifespan was determined using the CO breath test, and Hemoglobin glycation variation index (HGI) was calculated from the difference between measured and estimated HbA1c (eHbA1c). Model efficacy was evaluated using AUC, accuracy, sensitivity, and specificity.ResultsAn inflection in the HGI-RBC lifespan model occurred at 66 days, with HbA1c underestimation when RBC lifespan was below 90 days, notably in the ≤ 66 days group. This underestimation increased the risk of cardiovascular and peripheral neuropathy complications. To rectify the impact of the shorter RBC lifespan in T2DM patients, the correction formula was established as HbA1c(c) = -0.05629×RBC lifespan + 1.127×HbA1c + 3.178 (R = 0.7360) in the ≤ 66 day lifespan group and HbA1c(c) = -0.004772 × RBC lifespan + 0.7569 × HbA1c + 2.394 (R = 0.7344) in the 67 to 89 day group. The corrected HbA1c models exhibited satisfactory predictive performance in all cohorts.ConclusionsAccurate adjustment for the effects of RBC lifespan on HbA1c values in T2DM patients is expected to enhance blood glucose management and the efficacious prevention and treatment of diabetes-associated complications.Clinical Trial RegistrationChu Hsien-I Memorial Hospital of Tianjin Medical University, identifier ChiCTR2100046557.https://www.frontiersin.org/articles/10.3389/fendo.2025.1500660/fullglycosylated hemoglobin (HbA1c)hemoglobin glycation index (HGI)red blood cell lifespantype 2 diabetes mellituscorrection model
spellingShingle Li Zhang
Li Zhang
Ximan Gao
Ximan Gao
Xuying Meng
Xuying Meng
Guangyang Ma
Guangyang Ma
Jing Li
Jing Li
Weilin Wang
Weilin Wang
Sisi Chen
Sisi Chen
Yongjian Ma
Pei Yu
Pei Yu
Saijun Zhou
Saijun Zhou
Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verification
Frontiers in Endocrinology
glycosylated hemoglobin (HbA1c)
hemoglobin glycation index (HGI)
red blood cell lifespan
type 2 diabetes mellitus
correction model
title Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verification
title_full Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verification
title_fullStr Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verification
title_full_unstemmed Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verification
title_short Rectify the impact of shorter red blood cell lifespan upon HbA1c detection values in T2DM patients: modeling and internal-external verification
title_sort rectify the impact of shorter red blood cell lifespan upon hba1c detection values in t2dm patients modeling and internal external verification
topic glycosylated hemoglobin (HbA1c)
hemoglobin glycation index (HGI)
red blood cell lifespan
type 2 diabetes mellitus
correction model
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1500660/full
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