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Huang X, Huang L, Tao H, Ren M, Yan L. Nonlinear association between hemoglobin glycation index and mortality in ischemic stroke Patients: Insights from the MIMIC-IV database. Diabetes Res Clin Pract 2025; 224:112105. [PMID: 40096948 DOI: 10.1016/j.diabres.2025.112105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/02/2025] [Accepted: 03/13/2025] [Indexed: 03/19/2025]
Abstract
AIMS Hemoglobin glycation index (HGI) is closely associated with adverse outcomes in several diseases. However, few studies have investigated the correlation between HGI and prognosis in patients with critical ischemic stroke. METHODS A cohort of patients was established from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Kaplan-Meier analysis, multivariate regression models, and restricted cubic splines (RCS) were used to investigate the associations between HGI and different outcomes. Mediation models were constructed to determine the mediating role of white blood cell (WBC) counts. RESULTS This study included 2,332 participants. In-hospital mortality differs significantly across HGI groups (24.43 %, 11.82 %, and 10.14 %, P < 0.001). Multivariate regression analyses found that lower HGI was significantly associated with greater mortality risk. Nonlinear analyses revealed an L-shaped association between HGI and short-term mortality (30-day and in-hospital), while a reverse J-shaped relationship emerged for long-term (365-day) mortality. Mediation analysis revealed that WBC counts mediated the association with proportions (%) of 33.73, 19.65, and 30.00, respectively. CONCLUSION Lower HGI is consistently related to poorer outcomes in patients with critical ischemic stroke. Higher HGI could be a protective factor in the short term but might increase mortality risk in the long term. WBC counts significantly mediate the association.
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Affiliation(s)
- Xuhang Huang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China
| | - Lejun Huang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China
| | - Haoran Tao
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China
| | - Meng Ren
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China.
| | - Li Yan
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China.
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Ding H, Kang T, Gao W, Wang Q, Liu S, Zhang X, Yu J. Exploring the association between hemoglobin glycation index and cognitive function in older adults with hypertension: a cross-sectional study. BMC Geriatr 2025; 25:331. [PMID: 40361002 PMCID: PMC12070573 DOI: 10.1186/s12877-025-05999-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND The Hemoglobin Glycation Index (HGI) quantifies the difference between the actual and expected values of glycosylated hemoglobin (HbA1c), a marker that has been closely linked to various adverse health outcomes. Nonetheless, a significant gap exists in the current literature concerning the association between HGI and cognitive function. This study aims at testing such association in older adults with hypertension, a topic that has not yet been extensively investigated. METHODS A linear regression model between glycated hemoglobin A1c (HbA1c) levels and fasting plasma glucose (FPG) was constructed for the calculation of the HGI. The cross-sectional study focused on evaluating the cognitive function of hypertensive individuals (≥ 60 years old), based on the data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES), by using a series of standardized tests, including the Word List Learning (CERAD-WL) and Delayed Recall (CERAD-DR) tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Weighted logistic and linear regression models served for evaluating the effect of HGI on hypertensive patients' cognitive function. Restricted cubic spline (RCS) curves assisted in detecting the underlying nonlinear associations between HGI and cognitive outcomes. Furthermore, subgroup analyses and interaction tests were performed to gain deeper insights into these associations. RESULTS The study included 1023 participants ≥ 60 years old from 2011 to 2014 NHANES. Higher HGI was accompanied by lower DSST score (P = 0.009). In the fully adjusted model, participants in the highest quartile (Q4) of HGI possessed a lower DSST score (β = -4.50, 95% CI -8.10- -0.88) versus the lowest quartile (Q1), and were more likely to exhibit low cognitive function as evaluated by the DSST (OR = 2.21, 95% CI 0.98-5.03). According to the results from RCS analysis, HGI presented a linear relevance to cognitive function scores in older adults with hypertension. There is no interaction between HGI and the stratifying variables (sex, age, BMI, alcohol consumption, and smoking status). CONCLUSION High HGI was an important risk factor leading to reduced cognitive performance in hypertensive patients, ensuring HGI to be used for effectively predicting patients' cognitive decline.
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Affiliation(s)
- Hong Ding
- Department of Cardiovascular Medicine, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Tingyue Kang
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Wenbo Gao
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Qi Wang
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Shu Liu
- Department of Cardiovascular Medicine, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Xiaowei Zhang
- Department of Cardiovascular Medicine, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China.
| | - Jing Yu
- Department of Cardiovascular Medicine, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China.
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Fatih N, Hughes A, Sudre CH, Chaturvedi N, Garfield V, Silverwood RJ, Ploubidis G, Parker TD, Lu K, Cash DM, Malone IB, Wong A, Barnes J, Richards M, Fox NC, Schott JM, James SN. Sex differences between mid-life glycaemic traits and brain volume at age 70: a population-based study. Eur J Endocrinol 2025; 192:K44-K49. [PMID: 40300998 PMCID: PMC12084807 DOI: 10.1093/ejendo/lvaf090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 03/31/2025] [Accepted: 04/28/2025] [Indexed: 05/01/2025]
Abstract
Higher HbA1c in mid-to-later life has been associated with smaller whole brain volume (WBV) in older women but not men. We explored whether this association was replicated using different markers of (i) glycaemic health [fasting glucose, insulin resistance (HOMA2-IR), and β-cell function (HOMA-%B)] and (ii) brain structure (white or grey matter volume). 453 participants (51% men) from the 1946 British Birth Cohort had glycaemic measures (at age 60-64) and MRI measures (at age ∼70). In women, higher fasting glucose and insulin resistance at age ∼60 were weakly associated with lower WBV at age ∼70 [eg, fasting glucose: β* = -0.07 (95% CI: -0.13, -0.01), P = .02]. No associations emerged for men for any glycaemic marker. HOMA-%B was not associated with brain outcomes in either sex. Women's later-life brain health may be more vulnerable to midlife hyperglycaemia.
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Affiliation(s)
- Nasri Fatih
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
| | - Alun Hughes
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
| | - Carole H Sudre
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
| | - Nishi Chaturvedi
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
| | - Victoria Garfield
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
- Department of Pharmacology & Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 7BE, United Kingdom
| | - Richard J Silverwood
- Centre for Longitudinal Studies, UCL Social Research Institute, University College London, London WC1H 0AL, United Kingdom
| | - George Ploubidis
- Centre for Longitudinal Studies, UCL Social Research Institute, University College London, London WC1H 0AL, United Kingdom
| | - Thomas D Parker
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
| | - Kirsty Lu
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
| | - David M Cash
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
| | - Ian B Malone
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
| | - Andrew Wong
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
| | - Josephine Barnes
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
| | - Marcus Richards
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
| | - Nick C Fox
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
- UK Dementia Research Institute at UCL, University College London, London NW1 3BT, United Kingdom
| | - Jonathan M Schott
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
| | - Sarah-Naomi James
- MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, London WC1E 7HB, United Kingdom
- Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London WC1N 3AR, United Kingdom
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Guo Z, Li Y, An S, Zheng J. Association between the haemoglobin glycation index and 30-day and 365-day mortality in patients with heart failure admitted to the intensive care unit. Diabetol Metab Syndr 2025; 17:87. [PMID: 40102933 PMCID: PMC11916851 DOI: 10.1186/s13098-025-01661-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 03/07/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND The hemoglobin glycation index (HGI) represents the difference between the observed and predicted values of haemoglobin A1c (HbA1c). However, the association between HGI and prognosis of heart failure (HF) is not completely clarified yet and requires more investigation. This study aimed to explore the connection between HGI and mortality in HF patients. METHODS The data for the study were derived from the MIMIC-IV database from 2008 to 2019, a publicly available clinical database in intensive care. A linear regression equation between HbA1c and fasting blood glucose (FBG) was established to calculate predicted HbA1c. The endpoints were 30-day and 365-day all-cause mortality. Kaplan-Meier analysis was utilized to compare survival rates across groups differentiated by their HGI levels. The Cox regression models and restricted cubic spline (RCS) analysis were utilized to analyze the association between HGI and mortality. RESULTS The study collected a total of 2846 patients with HF (40.1% male), of whom 305 patients (10.7%) died within 30 days and 954 patients (33.5%) died within 365 days. Kaplan-Meier curves revealed patients with higher HGI had significantly higher mortality risks (log-rank P < 0.001). A high HGI was significantly associated with 30-day mortality (adjusted HR [aHR]: 2.36, 95% CI: 1.74-3.20, P < 0.001) and 365-day mortality (aHR: 1.40, 95% CI: 1.16-1.68, P < 0.001) after adjustment for potential confounders. Likewise, each unit increase in the HGI correlated with a 1.42-fold higher risk of 30-day mortality (aHR: 1.42, 95% CI: 1.28-1.57, P < 0.001) and 1.19-fold higher risk of 365-day mortality (aHR: 1.19, 95% CI: 1.11-1.68, P < 0.001). RCS analysis suggested an L-shaped nonlinear association between HGI and clinical endpoints (P for nonlinearity < 0.001), with an inflection point value of - 1.295. Subgroup analysis and sensitivity analysis revealed that the correlation between HGI and 30-day and 365-day all-cause mortality remained consistent. CONCLUSIONS In ICU-admitted HF patients, HGI was independently associated with increased risks of 30-day and 365-day mortality and the identification of high HGI (> 0.709) provided a valuable tool for clinicians to detect high-risk populations. Integrating HGI into routine clinical practice might strengthen the prognosis-based decision making improve HF patient outcomes.
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Affiliation(s)
- Ziyu Guo
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Yike Li
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuoyan An
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China
| | - Jingang Zheng
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China.
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Dong H, Hu P, Wang J, Lu N. Serum magnesium and calcium were inversely associated with hemoglobin glycation index and triglyceride-glucose index in adults with coronary artery disease. Biol Trace Elem Res 2025; 203:1422-1430. [PMID: 38913294 DOI: 10.1007/s12011-024-04287-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 06/19/2024] [Indexed: 06/25/2024]
Abstract
Little is known about the associations of magnesium (Mg) and calcium (Ca) with hemoglobin glycation index (HGI) and triglyceride-glucose index (TyG) in adults. In this study, we examined the associations of serum Mg and Ca with HGI and TyG in adults with coronary artery disease (CAD). This hospital-based cross-sectional study included 10757 CAD patients with a mean age of 61.6 years. Serum concentrations of Mg and Ca were measured in clinical laboratory. Overall, serum Mg and Ca were inversely associated with HGI and TyG. In multivariable analyses, Mg and Ca were inversely associated with HGI (MgQ4 vs. Q3: -0.601 vs. -0.528; CaQ4 vs. Q1: -0.769 vs. -0.645). In terms of TyG, inverse associations of serum Mg and Ca with TyG were observed. The corresponding TyG values were 9.054 (vs. 9.099) for Mg and 9.068 (vs. 9.171) for Ca in the fourth quartile compared with the first quartile. Moreover, Mg, Ca or Mg/Ca ratio were also inversely associated with HbA1c and FBG. In path analysis, no mediating effects of obesity on "serum Mg (or Ca)- HGI (or TyG)" associations were observed. Generally, our study identified the inverse associations of the serum Mg and Ca levels with HGI and TyG in adults with CAD. Large sample longitudinal study, and particularly randomized controlled trials, are warranted to validate our findings and overcome the limitations of cross-sectional studies.
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Affiliation(s)
- Hongli Dong
- Department of Child Healthcare and Scientific Education Section, Affiliated Maternity & Child Health Care Hospital of Nantong University, Nantong, 226018, Jiangsu, People's Republic of China
| | - Ping Hu
- Image Center, Wuhan Asia Heart Hospital, Wuhan, 430022, Hubei, People's Republic of China
| | - Jie Wang
- Image Center, Wuhan Asia Heart Hospital, Wuhan, 430022, Hubei, People's Republic of China
| | - Nan Lu
- Department of Psycho-Cardiology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, 100029, People's Republic of China.
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Wu Y, Zhang B, Ma X, Yu P, Zhou S, Wang X. Novel indicator of microvascular complications in patients with type 2 diabetes mellitus and shortened erythrocyte lifespan: a multicenter cross-sectional analysis. Diabetol Metab Syndr 2025; 17:26. [PMID: 39844294 PMCID: PMC11752720 DOI: 10.1186/s13098-025-01591-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 01/11/2025] [Indexed: 01/24/2025] Open
Abstract
INTRODUCTION In this study, we assessed whether the ratio of glucose management index (GMI) to glycated albumin (GA) was linked to microvascular complications in patients with type 2 diabetes mellitus (T2DM) who also possessed a shortened erythrocyte lifespan. METHODS This study encompassed individuals from the Tianjin Diabetic Retinopathy Screening Cohort who completed continuous glucose monitoring and had an erythrocyte lifespan of under 90 days. Differences in GMI/GA were compared between the T2DM patients with or without microvascular complications, including diabetic kidney disease (DKD) and diabetic retinopathy (DR). The relationship between GMI/GA and microvascular complications (DKD and/or DR) was assessed by dividing GMI/GA into three groups based on tertiles. RESULTS Our study comprised 140 participants with T2DM (62 men and 78 women, with a median age of 67 years) with a median DM duration of 9.68 years, a mean glycated hemoglobin A1c (HbA1c) value of 7.10%, and a median GA value of 16.10%. As expected, the lower GMI/GA group exhibited higher HbA1c and GA (P < 0.001) with similar mean glucose levels (P = 0.099). GMI/GA values were significantly higher in participants without microvascular complications than in those with microvascular complications, including DKD and/or DR (P < 0.05). After adjusting for confounders, the lowest GMI/GA group (T1) had a 3.601-fold increased risk of microvascular complications (95% CI, 1.364-9.508, P = 0.010) and a 3.830-fold increased risk of DKD, specifically (95% CI, 1.364-12.222, P = 0.023) relative to the highest group (T3). CONCLUSION GMI/GA serves as a novel risk indicator for microvascular complications in T2DM, independent of HbA1c.
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Affiliation(s)
- Yunqi Wu
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, 300134, China
| | - Binshan Zhang
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, 300134, China
| | - Xin Ma
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, 300134, China
| | - Pei Yu
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, 300134, China.
- Department of Nephrology & Blood Purification Center, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
| | - Saijun Zhou
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, 300134, China.
| | - Xinli Wang
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, 300134, China.
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Paprocki JD, Macdonald PJ, Xu Y, Cheng A, Dunn TC, Tetin SY. Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals. Sci Rep 2025; 15:2661. [PMID: 39837851 PMCID: PMC11751187 DOI: 10.1038/s41598-024-74574-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 09/26/2024] [Indexed: 01/23/2025] Open
Abstract
Measurement of glycated hemoglobin (HbA1c) in human red blood cells plays a critical role in the diagnosis and treatment of diabetes mellitus. However, recent studies have suggested large variation in the relationship between average glucose levels and HbA1c, creating the need to understand glucose variability at the cellular level. Here, we devised a fluorescence-based method to quantitatively observe GLUT1-mediated intracellular glucose analog tracer uptake in individual RBCs utilizing microfluidics and confocal microscopy. For the first time, we demonstrate that intracellular/extracellular tracer percentages can be measured at the single cell level using the fluorescently labeled glucose analog, 2-NBDG. A small donor panel study indicates that the characteristic intracellular 2-NBDG percentages can statistically differ based on race (i.e., Caucasian/Hispanic vs Black). RBC intracellular glucose analog tracer 2-NBDG levels show significant variability both from cell-to-cell and from donor-to-donor. This specific transport mechanism will affect HbA1c formation in erythrocytes. This finding further supports a more personalized, and perhaps improved, diagnostic strategy for diabetes.
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Affiliation(s)
- Joel D Paprocki
- Applied Research and Technology, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL, 60064, USA
| | - Patrick J Macdonald
- Applied Research and Technology, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL, 60064, USA
| | - Yongjin Xu
- Clinical Affairs, Abbott Diabetes Care Inc, 1420 Harbor Bay Parkway, Alameda, CA, 94502, USA
| | - Alan Cheng
- Clinical Affairs, Abbott Diabetes Care Inc, 1420 Harbor Bay Parkway, Alameda, CA, 94502, USA
| | - Timothy C Dunn
- Clinical Affairs, Abbott Diabetes Care Inc, 1420 Harbor Bay Parkway, Alameda, CA, 94502, USA.
| | - Sergey Y Tetin
- Applied Research and Technology, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL, 60064, USA
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House JS, Breeyear JH, Akhtari FS, Evans V, Buse JB, Hempe J, Doria A, Mychaleckyi JC, Fonseca V, Shi M, Li C, Liu S, Kelly TN, Rotroff D, Motsinger-Reif AA. A genome-wide association study identifies genetic determinants of hemoglobin glycation index with implications across sex and ethnicity. Front Endocrinol (Lausanne) 2024; 15:1473329. [PMID: 39530122 PMCID: PMC11551017 DOI: 10.3389/fendo.2024.1473329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/03/2024] [Indexed: 11/16/2024] Open
Abstract
Introduction We investigated the genetic determinants of variation in the hemoglobin glycation index (HGI), an emerging biomarker for the risk of diabetes complications. Methods We conducted a genome-wide association study (GWAS) for HGI in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N = 7,913) using linear regression and additive genotype encoding on variants with minor allele frequency greater than 3%. We conducted replication analyses of top findings in the Atherosclerosis Risk in Communities (ARIC) study with inverse variance-weighted meta-analysis. We followed up with stratified GWAS analyses by sex and self-reported race. Results In ACCORD, we identified single nucleotide polymorphisms (SNPs) associated with HGI, including a peak with the strongest association at the intergenic SNP rs73407935 (7q11.22) (P = 5.8e-10) with a local replication in ARIC. In black individuals, the variant rs10739419 on chromosome 9 in the Whirlin (WHRN) gene formally replicated (meta-P = 2.2e-9). The SNP-based heritability of HGI was 0.39 (P< 1e-10). HGI had significant sex-specific associations with SNPs in or near GALNT11 in women and HECW2 in men. Finally, in Hispanic participants, we observed genome-wide significant associations with variants near USF1 and NXNL2/SPIN1. Discussion Many HGI-associated SNPs were distinct from those associated with fasting plasma glucose or HbA1c, lending further support for HGI as a distinct biomarker of diabetes complications. The results of this first evaluation of the genetic etiology of HGI indicate that it is highly heritable and point to heterogeneity by sex and race.
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Affiliation(s)
- John S. House
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States
| | - Joseph H. Breeyear
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States
| | - Farida S. Akhtari
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States
| | - Violet Evans
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States
| | - John B. Buse
- Division of Endocrinology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - James Hempe
- Department of Pediatrics, Louisiana State University School of Medicine, New Orleans, LA, United States
| | - Alessandro Doria
- Section on Genetics and Epidemiology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA, United States
| | - Josyf C. Mychaleckyi
- Center of Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Vivian Fonseca
- Section of Endocrinology, School of Medicine, Tulane University, New Orleans, LA, United States
| | - Mengyao Shi
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States
| | - Changwei Li
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States
| | - Shuqian Liu
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States
| | - Tanika N. Kelly
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States
- Department of Health Policy and Management, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States
- Tulane University Translational Science Institute, New Orleans, LA, United States
| | - Daniel Rotroff
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
- Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, United States
- Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, United States
| | - Alison A. Motsinger-Reif
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States
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Lin Z, He J, Yuan S, Song C, Bian X, Yang M, Dou K. Hemoglobin glycation index and cardiovascular outcomes in patients with diabetes and coronary artery disease: insights from a large cohort study. Nutr Diabetes 2024; 14:69. [PMID: 39191777 DOI: 10.1038/s41387-024-00318-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 07/11/2024] [Accepted: 07/16/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND/OBJECTIVES The hemoglobin glycation index (HGI) has been demonstrated to serve as a substitute for the individual bias in glycosylated hemoglobin A1c (HbA1c). Our objective was to assess the correlation between HGI and cardiovascular (CV) outcomes in patients with diabetes and coronary artery disease (CAD). SUBJECTS/METHODS We sequentially recruited 11921 patients with diabetes and CAD at Fuwai Hospital. The patients were categorized into five groups based on their HGI quintiles, ranging from Q1 to Q5. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), which included CV death and nonfatal myocardial infarction. RESULTS During the median 3-year follow-up, 327 (2.7%) MACEs were observed. A U-shaped relationship between HGI and 3-year MACEs was demonstrated by restricted cubic spline (RCS) after multivariable adjustment (nonlinear P = 0.014). The Kaplan-Meier curves demonstrated that the Q2 group had the lowest risk of MACE (P = 0.006). When comparing the HGI Q2 group, multivariable Cox regression models showed that both low (Q1) and high (Q4 or Q5) HGI were linked to a higher risk of MACEs (all P < 0.05). Patients with a low HGI (Q1) had a significantly increased risk of all-cause and CV death, with a 1.70-fold increase in both cases (both P < 0.05). CONCLUSIONS In individuals with diabetes and established CAD, HGI levels were found to have a U-shaped relationship with the occurrence of MACEs over a period of three years. Significantly, those with low HGI had an increased risk of CV death.
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Affiliation(s)
- Zhangyu Lin
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jining He
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sheng Yuan
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenxi Song
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohui Bian
- State Key Laboratory of Cardiovascular Disease, Beijing, China
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min Yang
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Kefei Dou
- State Key Laboratory of Cardiovascular Disease, Beijing, China.
- Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- National Clinical Research Center for Cardiovascular Diseases, Beijing, China.
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10
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Ren L, Yang J, Wu L, Gao Y, Zhou Z, Li P, Shen Z, Wu J, Li J, Zhang L. Capillary Glycated Hemoglobin A1c Percentiles and the Risk Factors Associated with Abnormal HbA1c among Chinese Children Aged 3-12 Years. Pediatr Diabetes 2024; 2024:8333590. [PMID: 40302958 PMCID: PMC12017142 DOI: 10.1155/2024/8333590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 07/07/2024] [Accepted: 07/09/2024] [Indexed: 05/02/2025] Open
Abstract
Objective Capillary glycated hemoglobin (HbA1c) may enhance screening for childhood prediabetes and diabetes, but variations in this parameter remain unclear. We aimed to develop percentiles of HbA1c and explore the influence of various variables on HbA1c level among Chinese children. Study Design and Methods. The data were derived from the Shanghai Children's Health and Nutrition Community-based Epidemiologic Survey (CHANCE). A total of 4,615 children aged 3-12 years were included. The capillary HbA1c level was measured using point-of-care (POC) testing analyzers. Abnormal HbA1c level was identified as HbA1c (%) value equal to or above the 95th percentile of the nomograms. Results The mean HbA1c value was 5.30% (SD = 0.50%). The age-specific 95th percentile thresholds of HbA1c (%) ranged from 5.9 to 6.2 among all children. In the whole participants, body mass index (BMI), total cholesterol (TC), outdoor activity frequency, and daily sleep duration were positively associated with high HbA1c. Among preschool-aged children, TC and sleep duration ≥10 hr per day were associated with increased risk of being in the higher HbA1c (both P < 0.05). Among the school-aged group, positive associations with HbA1c levels were identified for TC, living with grandparents, frequency of outdoor activity, and sleep duration (all P < 0.05). Conclusions The present study established capillary HbA1c percentiles based on a large sample of Chinese children among aged 3-12 years. Daily sleep duration and frequency of outdoor activity, BMI, and TC were found to be associated with high HbA1c. Actions of successful public strategies that focus on promoting a healthy lifestyle, including regular physical exercise to reduce weight among children, are needed. Key Points. We used POC testing for capillary HbA1c with a finger-stick sample which may offer an opportunity to enhance screening and early diagnosis for childhood and adolescent diabetes, which was suggested as an essential premise to determine the subject's glycemic status by the American Diabetes Association (ADA). Capillary HbA1c levels fluctuate during childhood, while there has been no population-based study on HbA1c reference values in Chinese youths.
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Affiliation(s)
- Longbing Ren
- Clinical Center for Intelligent Rehabilitation ResearchShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)Tongji University School of MedicineTongji University, Shanghai 201613, China
- Community Health Service Center of Anting Town Affiliated with Medical College of Tongji University, Shanghai 201805, China
| | - Jing Yang
- Clinical Center for Intelligent Rehabilitation ResearchShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)Tongji University School of MedicineTongji University, Shanghai 201613, China
- Community Health Service Center of Anting Town Affiliated with Medical College of Tongji University, Shanghai 201805, China
| | - Lezhou Wu
- Department of Biomedical and Health InformaticsChildren's Hospital of Philadelphia, Philadelphia 19147, PA, USA
| | - Yan Gao
- Community Health Service Center of Anting Town Affiliated with Medical College of Tongji University, Shanghai 201805, China
| | - Zhitong Zhou
- Clinical Center for Intelligent Rehabilitation ResearchShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)Tongji University School of MedicineTongji University, Shanghai 201613, China
| | - Pin Li
- Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai 201102, China
| | - Zhiping Shen
- Community Health Service Center of Anting Town Affiliated with Medical College of Tongji University, Shanghai 201805, China
| | - Juanli Wu
- Daqiao Community Health Service CenterTongji University School of Medicine Shanghai, Shanghai 200090, China
| | - Jue Li
- Clinical Center for Intelligent Rehabilitation ResearchShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)Tongji University School of MedicineTongji University, Shanghai 201613, China
- Community Health Service Center of Anting Town Affiliated with Medical College of Tongji University, Shanghai 201805, China
| | - Lijuan Zhang
- Clinical Center for Intelligent Rehabilitation ResearchShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)Tongji University School of MedicineTongji University, Shanghai 201613, China
- Community Health Service Center of Anting Town Affiliated with Medical College of Tongji University, Shanghai 201805, China
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11
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Wei X, Chen X, Zhang Z, Wei J, Hu B, Long N, Feng J, Luo C. Risk analysis of the association between different hemoglobin glycation index and poor prognosis in critical patients with coronary heart disease-A study based on the MIMIC-IV database. Cardiovasc Diabetol 2024; 23:113. [PMID: 38555454 PMCID: PMC10981833 DOI: 10.1186/s12933-024-02206-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 03/16/2024] [Indexed: 04/02/2024] Open
Abstract
BACKGROUND The hemoglobin glycation index (HGI) is the difference between the observed and predicted values of glycosylated hemoglobin (HbA1c), which is closely associated with a variety of poor prognoses. However, there are still no studies on the correlation between HGI and poor prognosis in patients with critical coronary artery disease. The purpose of this study was to analyze the correlation between HGI and all-cause mortality in patients with critical coronary artery disease using the MIMIC-IV database. METHODS The HGI was calculated by constructing a linear regression equation between HbA1c and fasting plasma glucose (FPG). A Kaplan‒Meier survival analysis model was constructed based on the HGI quartiles to clarify the differences in all-cause mortality rates between groups, and the log-rank test was used to assess the differences between groups. The hazard ratio (HR) of HGI as a risk factor for outcome events was assessed using the Cox proportional risk model and restricted cubic spline (RCS), with the Q2 group serving as the reference group. RESULTS A total of 5260 patients were included in this study. The 30-day mortality rate of the patients was 4.94% and the mortality rate within 365 days was 13.12%. A low HGI was significantly associated with 30-day mortality (HR, 1.96; 95% CI, (1.38, 2.78); P < 0.001) and 365-day mortality (HR, 1.48; 95% CI, (1.19, 1.85); P < 0.001) in patients with critical coronary artery disease in the completely adjusted Cox proportional risk model. In addition, high levels of HGI were associated with 365-day mortality (HR, 1.31; 95% CI, (1.02, 1.69); P < 0.05). RCS analysis revealed a U-shaped relationship between HGI and outcome events. According to the stratified analysis, the interaction test revealed that the correlation between HGI and outcome events remained stable. CONCLUSION There was a significant correlation between HGI and all-cause mortality in patients with critical coronary artery disease, particularly in those with low HGI. HGI can be used as a potential indicator for assessing the short- and long-term risk of mortality in such patients.
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Affiliation(s)
- Xing Wei
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Xinghua Chen
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
- Intensive Care Unit, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, China
| | - Zhipeng Zhang
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Jing Wei
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Ben Hu
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Nv Long
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Jun Feng
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Chunmiao Luo
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China.
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China.
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12
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Wang Y, Liu H, Hu X, Wang A, Wang A, Kang S, Zhang L, Gu W, Dou J, Mu Y, Chen K, Wang W, Lyu Z. Association between hemoglobin glycation index and 5-year major adverse cardiovascular events: the REACTION cohort study. Chin Med J (Engl) 2023; 136:2468-2475. [PMID: 37265382 PMCID: PMC10586840 DOI: 10.1097/cm9.0000000000002717] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.
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Affiliation(s)
- Yuhan Wang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Hongzhou Liu
- Department of Endocrinology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiaodong Hu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Anping Wang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Anning Wang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Shaoyang Kang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Lingjing Zhang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Weijun Gu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jingtao Dou
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yiming Mu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Kang Chen
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Weiqing Wang
- Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Zhaohui Lyu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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13
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Sakane N, Hirota Y, Yamamoto A, Miura J, Takaike H, Hoshina S, Toyoda M, Saito N, Hosoda K, Matsubara M, Tone A, Kawashima S, Sawaki H, Matsuda T, Domichi M, Suganuma A, Sakane S, Murata T. Factors associated with hemoglobin glycation index in adults with type 1 diabetes mellitus: The FGM-Japan study. J Diabetes Investig 2023; 14:582-590. [PMID: 36789495 PMCID: PMC10034957 DOI: 10.1111/jdi.13973] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 12/22/2022] [Accepted: 12/24/2022] [Indexed: 02/16/2023] Open
Abstract
AIMS/INTRODUCTION The discrepancy between HbA1c and glucose exposure may have significant clinical implications; however, the association between the hemoglobin glycation index (HGI) and clinical parameters in type 1 diabetes remains controversial. This study aimed to find the factors associated with HGI (laboratory HbA1c - predicted HbA1c derived from the continuous glucose monitoring [CGM]). MATERIALS AND METHODS We conducted a cross-sectional study of adults with type 1 diabetes (n = 211, age 50.9 ± 15.2 years old, female sex = 59.2%, duration of CGM use = 2.1 ± 1.0 years). All subjects wore the CGM for 90 days before HbA1c measurement. Data derived from the FreeStyle Libre sensor were used to calculate the glucose management indicator (GMI) and glycemic variability (GV) parameters. HGI was defined as the difference between the GMI and the laboratory HbA1c levels. The participants were divided into three groups according to the HGI tertile (low, moderate, and high). Multivariate regression analyses were performed. RESULTS The female sex ratio, HbA1c, and % coefficient of variation (%CV) significantly increased over the HGI tertile, while eGFR and Hb decreased over the HGI tertile. In multivariate analysis, the factors associated with HGI were %CV and eGFR, after adjusting for HbA1c level and sex (R2 = 0.44). CONCLUSIONS This study demonstrated that HGI is associated with female sex, eGFR, and some glycemic variability indices, independently of HbA1c. Minimizing glycemic fluctuations might reduce HGI. This information provides diabetic health professionals and patients with personalized diabetes management for adults with type 1 diabetes.
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Affiliation(s)
- Naoki Sakane
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Yushi Hirota
- Division of Diabetes and Endocrinology, The Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Akane Yamamoto
- Division of Diabetes and Endocrinology, The Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Junnosuke Miura
- Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Hiroko Takaike
- Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Sari Hoshina
- Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
| | - Masao Toyoda
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Nobumichi Saito
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Kiminori Hosoda
- Division of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Masaki Matsubara
- Division of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center, Osaka, Japan
- Department of General Medicine, Nara Medical University, Nara, Japan
| | - Atsuhito Tone
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | | | - Hideaki Sawaki
- Sawaki Internal Medicine and Diabetes Clinic, Osaka, Japan
| | | | - Masayuki Domichi
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Akiko Suganuma
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Seiko Sakane
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Takashi Murata
- Department of Clinical Nutrition, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
- Diabetes Center, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
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14
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Abstract
Diabetes mellitus is the ninth leading cause of mortality worldwide. It is a complex disease that manifests as chronic hyperglycemia. Glucose exposure causes biochemical changes at the proteome level as reflected in accumulation of glycated proteins. A prominent example is hemoglobin A1c (HbA1c), a glycated protein widely accepted as a diabetic indicator. Another emerging biomarker is glycated albumin which has demonstrated utility in situations where HbA1c cannot be used. Other proteins undergo glycation as well thus impacting cellular function, transport and immune response. Accordingly, these glycated counterparts may serve as predictors for diabetic complications and thus warrant further inquiry. Fortunately, modern proteomics has provided unique analytic capability to enable improved and more comprehensive exploration of glycating agents and glycated proteins. This review broadly covers topics from epidemiology of diabetes to modern analytical tools such as mass spectrometry to facilitate a better understanding of diabetes pathophysiology. This serves as an attempt to connect clinically relevant questions with findings of recent proteomic studies to suggest future avenues of diabetes research.
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Affiliation(s)
- Aleks Shin
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States
| | - Shawn Connolly
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States
| | - Kuanysh Kabytaev
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States.
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15
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Wang RC, Lee EE, De Simone N, Kathote G, Primeaux S, Avila A, Yu DM, Johnson M, Good LB, Jakkamsetti V, Sarode R, Holland AA, Pascual JM. Red blood cells as glucose carriers to the human brain: Modulation of cerebral activity by erythrocyte exchange transfusion in Glut1 deficiency (G1D). J Cereb Blood Flow Metab 2023; 43:357-368. [PMID: 36523131 PMCID: PMC9941860 DOI: 10.1177/0271678x221146121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 11/08/2022] [Accepted: 11/14/2022] [Indexed: 12/23/2022]
Abstract
Red blood cells circulating through the brain are briefly but closely apposed to the capillary endothelium. We hypothesized that this contact provides a nearly direct pathway for metabolic substrate transfer to neural cells that complements the better characterized plasma to endothelium transfer. While brain function is considered independent of normal fluctuations in blood glucose concentration, this is not borne out by persons with glucose transporter I (GLUT1) deficiency (G1D). In them, encephalopathy is often ameliorated by meal or carbohydrate administration, and this enabled us to test our hypothesis: Since red blood cells contain glucose, and since the red cells of G1D individuals are also deficient in GLUT1, replacing them with normal donor cells via exchange transfusion could augment erythrocyte to neural cell glucose transport via mass action in the setting of unaltered erythrocyte count or plasma glucose abundance. This motivated us to perform red blood cell exchange in 3 G1D persons. There were rapid, favorable and unprecedented changes in cognitive, electroencephalographic and quality-of-life measures. The hypothesized transfer mechanism was further substantiated by in vitro measurement of direct erythrocyte to endothelial cell glucose flux. The results also indicate that the adult intellect is capable of significant enhancement without deliberate practice. ClinicalTrials.gov registration: NCT04137692 https://clinicaltrials.gov/ct2/show/NCT04137692.
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Affiliation(s)
- Richard C Wang
- Department of Dermatology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Eunice E Lee
- Department of Dermatology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Nicole De Simone
- Department of Pathology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Gauri Kathote
- Rare Brain Disorders Program, The University of Texas
Southwestern Medical Center, Dallas, Texas, USA
- Department of Neurology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Sharon Primeaux
- Rare Brain Disorders Program, The University of Texas
Southwestern Medical Center, Dallas, Texas, USA
- Department of Neurology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Adrian Avila
- Rare Brain Disorders Program, The University of Texas
Southwestern Medical Center, Dallas, Texas, USA
- Department of Neurology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Dong-Min Yu
- Department of Dermatology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Mark Johnson
- Department of Neurology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Levi B Good
- Rare Brain Disorders Program, The University of Texas
Southwestern Medical Center, Dallas, Texas, USA
- Department of Neurology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Vikram Jakkamsetti
- Rare Brain Disorders Program, The University of Texas
Southwestern Medical Center, Dallas, Texas, USA
- Department of Neurology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Ravi Sarode
- Departments of Pathology and Internal Medicine, The University
of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Alice Ann Holland
- Department of Psychiatry, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
| | - Juan M Pascual
- Rare Brain Disorders Program, The University of Texas
Southwestern Medical Center, Dallas, Texas, USA
- Department of Neurology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
- Department of Physiology, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
- Department of Pediatrics, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
- Eugene McDermott Center for Human Growth &
Development/Center for Human Genetics, The University of Texas Southwestern
Medical Center, Dallas, Texas, USA
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16
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Loyola-Leyva A, Loyola-Rodríguez JP, Barquera S, González FJ, Camacho-Lopez S, Terán-Figueroa Y. Differences in erythrocytes size and shape in prediabetes and diabetes assessed by two microscopy techniques and its association with dietary patterns. Pilot study. Microsc Res Tech 2022; 85:3726-3735. [PMID: 36165223 DOI: 10.1002/jemt.24238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 08/08/2022] [Accepted: 09/03/2022] [Indexed: 11/06/2022]
Abstract
Hemorheology and microcirculation alterations are caused by erythrocyte size and shape (ESS) modifications. People´s diets can alter erythrocyte functions and membrane fluidity by changing cell membrane components. The aim was to identify differences in ESS obtained by scanning electron (SEM) and atomic force microscopy (AFM) in people with prediabetes and type 2 diabetes (T2DM) and assess their relationship with dietary patterns. The study population included 31 participants (14 healthy, 11 with prediabetes, and 6 with T2DM). Dietary intake was assessed by a food frequency questionnaire, and dietary patterns were obtained using principal component analysis. ESS (diameter, height, axial ratio, thickness, and concave depth) were obtained by SEM and AFM. Differences in ESS between groups were observed with SEM (height) and AFM (height, axial ratio, and concave depth). T2DM presented smaller erythrocytes, more elongated and more altered forms. Two dietary patterns were identified: (1) Unhealthy: more refined cereals, high-fat dairy, fast food, sugary beverages, and fewer fruits, fish, seafood, low-fat dairy, and water. (2) Prudent: higher consumption of refined cereals, vegetables, poultry, low-fat dairy and nuts, and lower tortillas, eggs, high-fat dairy, and legumes. Tertile 3 of the Unhealthy dietary pattern had 80% of healthy participants. A difference in diameter and height (0.44 and 0.32 μm, respectively) obtained by SEM was observed when comparing tertile 2 (smaller erythrocytes) versus tertile 3 in the Unhealthy dietary pattern. SEM and AFM are excellent tools to assess ESS. Unhealthy dietary patterns might be associated with altered ESS. HIGHLIGHTS: SEM and AFM are excellent tools to assess erythrocyte size and shape modifications. Two dietary patterns were identified: healthy and prudent. Smaller erythrocytes were observed in the second tertile of the unhealthy pattern.
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Affiliation(s)
- Alejandra Loyola-Leyva
- Terahertz Science and Technology National Lab, Coordination for Innovation and Application of Science and Technology (Coordinación para la Innovación y Aplicación de la Ciencia y Tecnología, CIACyT), San Luis Potosí, Mexico
| | | | - Simon Barquera
- Center for Nutrition and Health Research, National Institute of Public Health (Instituto Nacional de Salud Pública), Morelos, Mexico
| | - Francisco Javier González
- Terahertz Science and Technology National Lab, Coordination for Innovation and Application of Science and Technology (Coordinación para la Innovación y Aplicación de la Ciencia y Tecnología, CIACyT), San Luis Potosí, Mexico
| | - Santiago Camacho-Lopez
- Department of Optics, Center for Scientific Research and Higher Education of Ensenada (Centro de Investigación Científica y de Educación Superior de Ensenada, CICESE), Ensenada, Baja California, Mexico
| | - Yolanda Terán-Figueroa
- Faculty of Nursing and Nutrition, Autonomous University of San Luis Potosí (Universidad Autónoma de San Luis Potosí, UASLP), San Luis Potosí, Mexico
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17
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Rescalli A, Varoni EM, Cellesi F, Cerveri P. Analytical Challenges in Diabetes Management: Towards Glycated Albumin Point-of-Care Detection. BIOSENSORS 2022; 12:bios12090687. [PMID: 36140073 PMCID: PMC9496022 DOI: 10.3390/bios12090687] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/20/2022] [Accepted: 08/23/2022] [Indexed: 11/16/2022]
Abstract
Diabetes mellitus is a worldwide-spread chronic metabolic disease that occurs when the pancreas fails to produce enough insulin levels or when the body fails to effectively use the secreted pancreatic insulin, eventually resulting in hyperglycemia. Systematic glycemic control is the only procedure at our disposal to prevent diabetes long-term complications such as cardiovascular disorders, kidney diseases, nephropathy, neuropathy, and retinopathy. Glycated albumin (GA) has recently gained more and more attention as a control biomarker thanks to its shorter lifespan and wider reliability compared to glycated hemoglobin (HbA1c), currently the “gold standard” for diabetes screening and monitoring in clinics. Various techniques such as ion exchange, liquid or affinity-based chromatography and immunoassay can be employed to accurately measure GA levels in serum samples; nevertheless, due to the cost of the lab equipment and complexity of the procedures, these methods are not commonly available at clinical sites and are not suitable to home monitoring. The present review describes the most up-to-date advances in the field of glycemic control biomarkers, exploring in particular the GA with a special focus on the recent experimental analysis techniques, using enzymatic and affinity methods. Finally, analysis steps and fundamental reading technologies are integrated into a processing pipeline, paving the way for future point-of-care testing (POCT). In this view, we highlight how this setup might be employed outside a laboratory environment to reduce the time from measurement to clinical decision, and to provide diabetic patients with a brand-new set of tools for glycemic self-monitoring.
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Affiliation(s)
- Andrea Rescalli
- Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy
- Correspondence: (A.R.); (E.M.V.)
| | - Elena Maria Varoni
- Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, 20122 Milan, Italy
- Correspondence: (A.R.); (E.M.V.)
| | - Francesco Cellesi
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, 20133 Milan, Italy
| | - Pietro Cerveri
- Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy
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18
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Abstract
A high hemoglobin glycation index (HGI) has been repeatedly associated with greater risk for hypoglycemia in people with diabetes and greater risk for chronic vascular disease in people with or without diabetes. This review explores how different sources of analytical and biological variation in HbA1c and blood glucose individually and collectively affect the clinical information value of HGI. We conclude that HGI is a complex quantitative trait that is a clinically practical biomarker of risk for both hypoglycemia and chronic vascular disease.
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Affiliation(s)
- James M Hempe
- Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
| | - Daniel S Hsia
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
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19
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Campbell MD, West DJ, O’Mahoney LL, Pearson S, Kietsiriroje N, Holmes M, Ajjan RA. The relative contribution of diurnal and nocturnal glucose exposures to HbA1c in type 1 diabetes males: a pooled analysis. J Diabetes Metab Disord 2022; 21:573-581. [PMID: 35673512 PMCID: PMC9167262 DOI: 10.1007/s40200-022-01015-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 02/28/2022] [Indexed: 11/25/2022]
Abstract
Purpose The exact contribution of daily glucose exposure to HbA1c in people with type 1 diabetes (T1D) remains controversial. We examined the contribution of pre- and postprandial glycaemia, nocturnal and early-morning glycaemia, and glycaemic variability to HbA1c levels in T1D. In this analysis, we used clinical data, namely age, BMI and HbA1c, as well as glycaemic metrics (24-h glycaemia, postprandial, nocturnal, early-morning glycaemia, wake-up glucose, and glycaemic variability) obtained over a four-week period of continuous glucose monitoring (CGM) wear in thirty-two males with T1D. Methods The trapezoid method was used estimate the incremental area under the glucose curve (iAUC) for 24-h, postprandial (3-h period following breakfast, lunch, and dinner, respectively), nocturnal (between 24:00–04:00 AM), and early-morning (2-h period 2-h prior to wake-up) glycaemia. Linear regression analysis was employed whereby CGM-derived glycaemic metrics were explanatory variables and HbA1c was the outcome. Results Thirty-two T1D males (mean ± SD: age 29 ± 4 years; HbA1c 7.3 ± 0.9% [56 ± 13 mmol/mol]; BMI 25.80 ± 5.01 kg/m2) were included in this analysis. In linear models adjusted for age and BMI, HbA1c was associated with 24-h mean glucose (r2 = 0.735, p < 0.001), SD (r2 = 0.643, p = 0.039), and dinner iAUC (r2 = 0.711, p = 0.001). CGM-derived metrics and non-glycaemic factors explained 77% of the variance in HbA1c, in which postprandial glucose accounted for 32% of the variance explained. The single greatest contributor to HbA1c was dinner iAUC resulting in 0.6%-point (~7 mmol/mol) increase in HbA1c per SD increase in dinner iAUC. Conclusions Using comprehensive CGM profiling, we show that postprandial glucose, specifically evening-time postprandial glucose, is the single largest contributing factor to HbA1c in T1D. Trial registration number NCT02204839 (July 30th 2014); NCT02595658 (November 3rd 2015).
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Affiliation(s)
- Matthew D. Campbell
- Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, SR1 3SD UK
- Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Daniel J. West
- Human Nutrition Research Centre, Newcastle University, Newcastle, UK
- Population Health Science Institute, Faculty of Medical Science, Newcastle University, Newcastle, UK
| | - Lauren L. O’Mahoney
- Diabetes Research Centre, Leicester General Hospital, University of Leicester, Leicester, UK
| | - Sam Pearson
- Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Noppadol Kietsiriroje
- Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Mel Holmes
- Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Ramzi A. Ajjan
- Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
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20
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Klein KR, Franek E, Marso S, Pieber TR, Pratley RE, Gowda A, Kvist K, Buse JB. Hemoglobin glycation index, calculated from a single fasting glucose value, as a prediction tool for severe hypoglycemia and major adverse cardiovascular events in DEVOTE. BMJ Open Diabetes Res Care 2021; 9:e002339. [PMID: 34819298 PMCID: PMC8614152 DOI: 10.1136/bmjdrc-2021-002339] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 10/31/2021] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Hemoglobin glycation index (HGI) is the difference between observed and predicted glycated hemoglobin A1c (HbA1c), derived from mean or fasting plasma glucose (FPG). In this secondary, exploratory analysis of data from DEVOTE, we examined: whether insulin initiation/titration affected the HGI; the relationship between baseline HGI tertile and cardiovascular and hypoglycemia risk; and the relative strengths of HGI and HbA1c in predicting these risks. RESEARCH DESIGN AND METHODS In DEVOTE, a randomized, double-blind, cardiovascular outcomes trial, people with type 2 diabetes received once per day insulin degludec or insulin glargine 100 units/mL. The primary outcome was time to first occurrence of a major adverse cardiovascular event (MACE), comprising cardiovascular death, myocardial infarction or stroke; severe hypoglycemia was a secondary outcome. In these analyses, predicted HbA1c was calculated using a linear regression equation based on DEVOTE data (HbA1c=0.01313 FPG (mg/dL) (single value)+6.17514), and the population data were grouped into HGI tertiles based on the calculated HGI values. The distributions of time to first event were compared using Kaplan-Meier curves; HRs and 95% CIs were determined by Cox regression models comparing risk of MACE and severe hypoglycemia between tertiles. RESULTS Changes in HGI were observed at 12 months after insulin initiation and stabilized by 24 months for the whole cohort and insulin-naive patients. There were significant differences in MACE risk between baseline HGI tertiles; participants with high HGI were at highest risk (low vs high, HR: 0.73 (0.61 to 0.87)95% CI; moderate vs high, HR: 0.67 (0.56 to 0.81)95% CI; p<0.0001). No significant differences between HGI tertiles were observed in the risk of severe hypoglycemia (p=0.0911). With HbA1c included within the model, HGI no longer significantly predicted MACE. CONCLUSIONS High HGI was associated with a higher risk of MACE; this finding is of uncertain significance given the association of HGI with insulin initiation and HbA1c. TRIAL REGISTRATION NUMBER NCT01959529.
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Affiliation(s)
- Klara R Klein
- Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
| | - Edward Franek
- Mossakowski Medical Research Centre, Polish Academy of Sciences, Central Clinical Hospital MSW, Warsaw, Poland
| | - Steven Marso
- HCA Midwest Health Heart and Vascular Institute, Overland Park, Kansas, USA
| | - Thomas R Pieber
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Richard E Pratley
- AdventHealth Translational Research Institute, Orlando, Florida, USA
| | | | | | - John B Buse
- Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
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21
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Kohzuma T, Tao X, Koga M. Glycated albumin as biomarker: Evidence and its outcomes. J Diabetes Complications 2021; 35:108040. [PMID: 34507877 DOI: 10.1016/j.jdiacomp.2021.108040] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 08/25/2021] [Accepted: 08/25/2021] [Indexed: 02/01/2023]
Abstract
Glycemic control markers are important for the diagnosis and treatment of diabetes. Hemoglobin A1c (A1C) is an important marker that is mandatory in routine medical examinations; however, it is well known that it has some limitations. In this review, we focus on the limitation of A1C and introduce a relatively new marker, glycated albumin (GA), which can be used to complement A1C. First, for a better understanding of the characteristics of each marker, we sort the similarities and differences of glycemic control markers as well as the characteristics of each marker. Second, we point out the limitation of A1C, introduce GA as an alternative indicator, and discuss the limitations of GA. Finally, we summarize important evidence regarding the utility of GA. We hope that this review provides useful information that permits more effective usage of GA as well as other glycemic control markers.
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Affiliation(s)
| | - Xinran Tao
- Asahi Kasei Pharma Corporation, Tokyo, Japan
| | - Masafumi Koga
- Department of Internal Medicine, Hakuhokai Central Hospital, Hyogo, Japan
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22
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Xu Y, Bergenstal RM, Dunn TC, Ajjan RA. Addressing shortfalls of laboratory HbA 1c using a model that incorporates red cell lifespan. eLife 2021; 10:69456. [PMID: 34515636 PMCID: PMC8437432 DOI: 10.7554/elife.69456] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 08/24/2021] [Indexed: 12/19/2022] Open
Abstract
Laboratory HbA1c does not always predict diabetes complications and our aim was to establish a glycaemic measure that better reflects intracellular glucose exposure in organs susceptible to complications. Six months of continuous glucose monitoring data and concurrent laboratory HbA1c were evaluated from 51 type 1 diabetes (T1D) and 80 type 2 diabetes (T2D) patients. Red blood cell (RBC) lifespan was estimated using a kinetic model of glucose and HbA1c, allowing the calculation of person-specific adjusted HbA1c (aHbA1c). Median (IQR) RBC lifespan was 100 (86–102) and 100 (83–101) days in T1D and T2D, respectively. The median (IQR) absolute difference between aHbA1c and laboratory HbA1c was 3.9 (3.0–14.3) mmol/mol [0.4 (0.3–1.3%)] in T1D and 5.3 (4.1–22.5) mmol/mol [0.5 (0.4–2.0%)] in T2D. aHbA1c and laboratory HbA1c showed clinically relevant differences. This suggests that the widely used measurement of HbA1c can underestimate or overestimate diabetes complication risks, which may have future clinical implications.
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Affiliation(s)
- Yongjin Xu
- Abbott Diabetes Care, Alameda, United States
| | - Richard M Bergenstal
- International Diabetes Center, Park Nicollet, HealthPartners, Minneapolis, United States
| | | | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
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23
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Chalew S, Delamater AM, Washington S, Bhat J, Franz D, Gomez R, Felipe D, Tieh P, Finger L. Can Innovative Technologies Overcome HbA1c Disparity for African-American Youth with Type 1 Diabetes? J Diabetes Sci Technol 2021; 15:1069-1075. [PMID: 34137288 PMCID: PMC8442203 DOI: 10.1177/19322968211021386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Achieving normal or near-normal glycemic control as reflected by HbA1c levels in patients with type 1 diabetes (T1D) is important for preventing the development and progression of chronic complications. Despite delineation and dissemination of HbA1c management targets and advances in insulin pharmacology, insulin delivery systems, and glucose monitoring, the majority of children with T1D do not achieve HbA1c goals. In particular, African Americans are more likely not to reach HbA1c goals and have persistently higher HbA1c than Non-Hispanic Whites. Availability of pumps and other technology has not eliminated the disparity in HbA1c. Multiple factors play a role in the persisting racial disparity in HbA1c outcome. The carefully designed application and deployment of new technology to help the patient/family and facilitate the supportive role of the diabetes management team may be able to overcome racial disparity in glycemic outcome and improve patient quality of life.
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Affiliation(s)
- Stuart Chalew
- Department of Pediatrics,
Division of Pediatric Endocrinology and Diabetes, School of Medicine,
Louisiana State University Health Sciences Center, Children’s Hospital of
New Orleans, New Orleans, LA, USA
- Stuart Chalew, MD, Department of
Pediatrics, Endocrinology and Diabetes, School of Medicine, Louisiana
State University Health Sciences Center, Children’s Hospital of New
Orleans, 200 Henry Clay Avenue, New Orleans, LA 70118, USA.
| | - Alan M. Delamater
- Department of Pediatrics,
University of Miami Miller School of Medicine, Miami, FL, USA
| | - Sonja Washington
- Endocrinology and Diabetes, The
Children’s Hospital of New Orleans, New Orleans, LA, USA
| | - Jayalakshmi Bhat
- Department of Pediatrics,
Division of Pediatric Endocrinology and Diabetes, School of Medicine,
Louisiana State University Health Sciences Center, Children’s Hospital of
New Orleans, New Orleans, LA, USA
| | - Diane Franz
- Department of Psychology, The
Children’s Hospital of New Orleans, New Orleans, LA, USA
| | - Ricardo Gomez
- Department of Pediatrics,
Division of Pediatric Endocrinology and Diabetes, School of Medicine,
Louisiana State University Health Sciences Center, Children’s Hospital of
New Orleans, New Orleans, LA, USA
| | - Dania Felipe
- Department of Pediatrics,
Division of Pediatric Endocrinology and Diabetes, School of Medicine,
Louisiana State University Health Sciences Center, Children’s Hospital of
New Orleans, New Orleans, LA, USA
| | - Peter Tieh
- Department of Pediatrics,
Division of Pediatric Endocrinology and Diabetes, School of Medicine,
Louisiana State University Health Sciences Center, Children’s Hospital of
New Orleans, New Orleans, LA, USA
| | - Laurie Finger
- Endocrinology and Diabetes, The
Children’s Hospital of New Orleans, New Orleans, LA, USA
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24
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Wondimu ET, Zhang Q, Jin Z, Fu M, Torregrossa R, Whiteman M, Yang G, Wu L, Wang R. Effect of hydrogen sulfide on glycolysis-based energy production in mouse erythrocytes. J Cell Physiol 2021; 237:763-773. [PMID: 34346059 DOI: 10.1002/jcp.30544] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 07/06/2021] [Accepted: 07/24/2021] [Indexed: 11/08/2022]
Abstract
Hydrogen sulfide (H2 S) is a gasotransmitter that regulates both physiological and pathophysiological processes in mammalian cells. Recent studies have demonstrated that H2 S promotes aerobic energy production in the mitochondria in response to hypoxia, but its effect on anaerobic energy production has yet to be established. Glycolysis is the anaerobic process by which ATP is produced through the metabolism of glucose. Mammalian red blood cells (RBCs) extrude mitochondria and nucleus during erythropoiesis. These cells would serve as a unique model to observe the effect of H2 S on glycolysis-mediated energy production. The purpose of this study was to determine the effect of H2 S on glycolysis-mediated energy production in mitochondria-free mouse RBCs. Western blot analysis showed that the only H2 S-generating enzyme expressed in mouse RBCs is 3-mercaptopyruvate sulfurtransferase (MST). Supplement of the substrate for MST stimulated, but the inhibition of the same suppressed, the endogenous production of H2 S. Both exogenously administered H2 S salt and MST-derived endogenous H2 S stimulated glycolysis-mediated ATP production. The effect of NaHS on ATP levels was not affected by oxygenation status. On the contrary, hypoxia increased intracellular H2 S levels and MST activity in mouse RBCs. The mitochondria-targeted H2 S donor, AP39, did not affect ATP levels of mouse RBCs. NaHS at low concentrations (3-100 μM) increased ATP levels and decreased cell viability after 3 days of incubation in vitro. Higher NaHS concentrations (300-1000 μM) lowered ATP levels, but prolonged cell viability. H2 S may offer a cytoprotective effect in mammalian RBCs to maintain oxygen-independent energy production.
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Affiliation(s)
- Eden T Wondimu
- Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.,Department of Biology, Laurentian University, Sudbury, Ontario, Canada
| | - Quanxi Zhang
- Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.,School of Life Science, Shanxi University, Taiyuan, China
| | - Zhuping Jin
- Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.,School of Life Science, Shanxi University, Taiyuan, China
| | - Ming Fu
- Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.,School of Human Kinetics, Laurentian University, Sudbury, Ontario, Canada
| | - Roberta Torregrossa
- University of Exeter Medical School, Exeter, UK.,MitoRx Therapeutics, Oxford, UK
| | - Matthew Whiteman
- University of Exeter Medical School, Exeter, UK.,MitoRx Therapeutics, Oxford, UK
| | - Guangdong Yang
- Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.,Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada
| | - Lingyun Wu
- Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada.,School of Human Kinetics, Laurentian University, Sudbury, Ontario, Canada.,Health Sciences North Research Institute, Sudbury, Ontario, Canada
| | - Rui Wang
- Department of Biology, York University, Toronto, Ontario, Canada
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25
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Xu Y, Grimsmann JM, Karges B, Hofer S, Danne T, Holl RW, Ajjan RA, Dunn TC. Personal Glycation Factors and Calculated Hemoglobin A1c for Diabetes Management: Real-World Data from the Diabetes Prospective Follow-up (DPV) Registry. Diabetes Technol Ther 2021; 23:452-459. [PMID: 33395370 DOI: 10.1089/dia.2020.0553] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Background: Glycated hemoglobin A1c (HbA1c) is a key biomarker in the glycemic management of individuals with diabetes, but the relationship with glucose levels can be variable. A recent kinetic model has described a calculated HbA1c (cHbA1c) that is individual specific. Our aim was to validate the routine clinical use of this glucose metric in younger individuals with diabetes under real-life settings. Materials and Methods: We retrieved HbA1c and glucose data from the German-Austrian-Swiss-Luxembourgian diabetes follow-up (DPV) registry, which covers pediatric individuals with type 1 diabetes (T1D). The new glycemic measure, cHbA1c, uses two individual parameters identified by data sections that contain continuous glucose data between two laboratory HbA1c measurements. The cHbA1c was prospectively validated using longitudinal HbA1c data. Results: Continuous glucose monitoring data from 352 T1D individuals in 13 clinics were analyzed together with HbA1c that ranged between 4.9% and 10.6%. In the prospective analysis, absolute deviations of estimated HbA1c (eHbA1c), glucose management indicator (GMI), and cHbA1c compared with laboratory HbA1c were (median [interquartile range]): 1.01 (0.50, 1.75), 0.46 (0.21, 084) and 0.26 (0.12, 0.46), giving an average bias of 0.6, 0.4 and 0.0, respectively, in National Glycohemoglobin Standardization Program (NGSP) % unit. For eHbA1c and GMI only 25% and 54% of subjects were within ±0.5% of laboratory HbA1c values, whereas 82% of cHbA1c were within ±0.5% of laboratory HbA1c results. Conclusions: Our data show the superior performance of cHbA1c compared with eHbA1c and GMI at reflecting laboratory HbA1c. These data indicate that cHbA1c can be potentially used instead in laboratory HbA1c, at least in younger individuals with T1D.
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Affiliation(s)
- Yongjin Xu
- Clinical and Computational Research, Abbott Diabetes Care, Alameda, California, USA
| | - Julia M Grimsmann
- Institute of Epidemiology and Medical Biometry, Central Institute for Biomedical Technology, University of Ulm, Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Beate Karges
- Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Sabine Hofer
- Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Danne
- Diabetes Centre for Children and Adolescents, Children's and Youth Hospital "Auf der Bult," Hannover, Germany
| | - Reinhard W Holl
- Institute of Epidemiology and Medical Biometry, Central Institute for Biomedical Technology, University of Ulm, Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
| | - Timothy C Dunn
- Clinical and Computational Research, Abbott Diabetes Care, Alameda, California, USA
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26
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Chen Y, Pan Y, Feng Y, Li D, Man J, Feng L, Zhang D, Chen H, Chen H. Role of glucose in the repair of cell membrane damage during squeeze distortion of erythrocytes in microfluidic capillaries. LAB ON A CHIP 2021; 21:896-903. [PMID: 33432946 DOI: 10.1039/d0lc00411a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
The rapid development of portable precision detection methods and the crisis of insufficient blood supply worldwide has led scientists to study mechanical visualization features beyond the biochemical properties of erythrocytes. Combined evaluation of currently known biochemical biomarkers and mechanical morphological biomarkers will become the mainstream of single-cell detection in the future. To explore the mechanical morphology of erythrocytes, a microfluidic capillary system was constructed in vitro, with flow velocity and glucose concentration as the main variables, and the morphology and ability of erythrocytes to recover from deformation as the main objects of analysis. We showed the mechanical distortion of erythrocytes under various experimental conditions. Our results showed that glucose plays important roles in improving the ability of erythrocytes to recover from deformation and in repairing the damage caused to the cell membrane during the repeated squeeze process. These protective effects were also confirmed in in vivo experiments. Our results provide visual detection markers for single-cell chips and may be useful for future studies in cell aging.
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Affiliation(s)
- Yuanyuan Chen
- State Key Laboratory of Tribology, Mechanical Engineering Department, Tsinghua University, Beijing, 100084, China. and School of Mechanical Engineering and Automation, Beijing Advanced Innovation Center for Biomedical Engineering, Institute of Bionic and Micro-Nano Systems, Beihang University, Beijing, 100191, China
| | - Yunfan Pan
- State Key Laboratory of Tribology, Mechanical Engineering Department, Tsinghua University, Beijing, 100084, China.
| | - Yuzhen Feng
- Moleculaire Biofysica, Zernike Institute, Rijksuniversiteit Groningen, Nijenborgh 4, 9747 AG Groningen, Netherlands
| | - Donghai Li
- Advanced Medical Research Institute, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012, P.R China
| | - Jia Man
- Key Laboratory of High Efficiency and Clean Mechanical Manufacture of MOE, School of Mechanical Engineering, Key National Demonstration Center for Experimental Mechanical Engineering Education, Shandong University, Jinan 250061, PR China
| | - Lin Feng
- School of Mechanical Engineering and Automation, Beijing Advanced Innovation Center for Biomedical Engineering, Institute of Bionic and Micro-Nano Systems, Beihang University, Beijing, 100191, China
| | - Deyuan Zhang
- School of Mechanical Engineering and Automation, Beijing Advanced Innovation Center for Biomedical Engineering, Institute of Bionic and Micro-Nano Systems, Beihang University, Beijing, 100191, China
| | - Huawei Chen
- School of Mechanical Engineering and Automation, Beijing Advanced Innovation Center for Biomedical Engineering, Institute of Bionic and Micro-Nano Systems, Beihang University, Beijing, 100191, China
| | - Haosheng Chen
- State Key Laboratory of Tribology, Mechanical Engineering Department, Tsinghua University, Beijing, 100084, China.
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27
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Xu Y, Dunn TC, Ajjan RA. A Kinetic Model for Glucose Levels and Hemoglobin A1c Provides a Novel Tool for Individualized Diabetes Management. J Diabetes Sci Technol 2021; 15:294-302. [PMID: 31910672 PMCID: PMC8256073 DOI: 10.1177/1932296819897613] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Regular assessment of glycated hemoglobin (HbA1c) is central to the management of patients with diabetes. Estimated HbA1c (eHbA1c) from continuous glucose monitoring (CGM) has been proposed as a measure that reflects laboratory HbA1c. However, discrepancies between the two markers are common, limiting the clinical use of eHbA1c. Therefore, developing a glycemic maker that better reflects laboratory HbA1c will be highly relevant in diabetes management. METHODS Using CGM data from two previous clinical studies in 120 individuals with diabetes, we derived a novel kinetic model that takes into account red blood cell (RBC) turnover, cross-membrane glucose transport, and hemoglobin glycation processes to individualize the relationship between glucose levels and HbA1c. RESULTS Using CGM data and two laboratory HbA1c measurements, kinetic rate constants for RBC glycation and turnover were calculated. These rate constants were used to project future HbA1c, creating a new individualized glycemic marker, termed calculated HbA1c (cHbA1c). In contrast to eHbA1c, the new glycemic marker cHbA1c gave an accurate estimation of laboratory HbA1c across individuals. The model and data demonstrated a non-linear relationship between laboratory HbA1c and steady-state glucose and also showed that glycation status is modulated by age. CONCLUSION Our kinetic model offers mechanistic insights into the relationship between glucose levels and glycated hemoglobin. Therefore, the new glycemic marker does not only accurately reflect laboratory HbA1c but also provides novel concepts to explain the mechanisms for the mismatch between HbA1c and average glucose in some individuals, which has implications for future clinical management.
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Affiliation(s)
- Yongjin Xu
- Abbott Diabetes Care, Alameda, CA,
USA
- Yongjin Xu, PhD, Abbott Diabetes Care, 1360
South Loop Road, Alameda, CA 94502, USA.
| | | | - Ramzi A. Ajjan
- Leeds University, Leeds Institute of
Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
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28
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Rivera-Yañez N, Rivera-Yañez CR, Pozo-Molina G, Méndez-Catalá CF, Méndez-Cruz AR, Nieto-Yañez O. Biomedical Properties of Propolis on Diverse Chronic Diseases and Its Potential Applications and Health Benefits. Nutrients 2020; 13:E78. [PMID: 33383693 PMCID: PMC7823938 DOI: 10.3390/nu13010078] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/24/2020] [Accepted: 12/24/2020] [Indexed: 02/06/2023] Open
Abstract
The use of alternative medicine products has increased tremendously in recent decades and it is estimated that approximately 80% of patients globally depend on them for some part of their primary health care. Propolis is a beekeeping product widely used in alternative medicine. It is a natural resinous product that bees collect from various plants and mix with beeswax and salivary enzymes and comprises a complex mixture of compounds. Various biomedical properties of propolis have been studied and reported in infectious and non-infectious diseases. However, the pharmacological activity and chemical composition of propolis is highly variable depending on its geographical origin, so it is important to describe and study the biomedical properties of propolis from different geographic regions. A number of chronic diseases, such as diabetes, obesity, and cancer, are the leading causes of global mortality, generating significant economic losses in many countries. In this review, we focus on compiling relevant information about propolis research related to diabetes, obesity, and cancer. The study of propolis could generate both new and accessible alternatives for the treatment of various diseases and will help to effectively evaluate the safety of its use.
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Affiliation(s)
- Nelly Rivera-Yañez
- Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (N.R.-Y.); (C.R.R.-Y.)
| | - C. Rebeca Rivera-Yañez
- Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (N.R.-Y.); (C.R.R.-Y.)
| | - Glustein Pozo-Molina
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (G.P.-M.); (C.F.M.-C.)
| | - Claudia F. Méndez-Catalá
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (G.P.-M.); (C.F.M.-C.)
| | - Adolfo R. Méndez-Cruz
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico;
| | - Oscar Nieto-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico
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Klein KR, Buse JB. The trials and tribulations of determining HbA 1c targets for diabetes mellitus. Nat Rev Endocrinol 2020; 16:717-730. [PMID: 33082551 PMCID: PMC11653296 DOI: 10.1038/s41574-020-00425-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/16/2020] [Indexed: 12/19/2022]
Abstract
Glycated haemoglobin (HbA1c) is considered the gold standard for predicting glycaemia-associated risks for the microvascular and macrovascular complications of diabetes mellitus over 5-10 years. The value of HbA1c in the care of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) is unassailable, yet HbA1c targets remain contentious. Guidelines from diabetes care organizations recommend conflicting HbA1c targets - generally between 6.5% and 8%. However, all such organizations advocate for individualization of HbA1c targets, leaving both health-care providers and their patients confused about what HbA1c target is appropriate in an individual patient. In this Review, we outline the landmark T1DM and T2DM trials that informed the current guidelines, we discuss the evidence that drives individualized HbA1c targets, we examine the limitations of HbA1c, and we consider alternatives for monitoring glycaemic control. Ultimately, in synthesizing this literature, we argue for an HbA1c target of <7% for most individuals, but emphasize the importance of helping patients determine their own personal goals and determinants of quality of life that are independent of a particular glycaemic target. We also recognize that as newer technologies and anti-hyperglycaemic therapies emerge, glycaemic targets will continue to evolve.
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Affiliation(s)
- Klara R Klein
- Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
| | - John B Buse
- Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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30
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Gordon DK, Hussain M, Kumar P, Khan S, Khan S. The Sickle Effect: The Silent Titan Affecting Glycated Hemoglobin Reliability. Cureus 2020; 12:e9685. [PMID: 32923278 PMCID: PMC7486097 DOI: 10.7759/cureus.9685] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 08/12/2020] [Indexed: 12/18/2022] Open
Abstract
Hemoglobin A1c (HbA1c) is a popular invaluable tool in the diagnosis of Type 2 diabetes for red blood cells (RBCs) with a lifespan of 120 days; however, many factors, including hemoglobinopathies, affect its accuracy. Sickle cell trait, primarily a benign medical condition, is a point mutation in only one of two beta-globin genes on chromosome 11. We performed a traditional review to identify how the sickle cell trait (SCT) affects the interpretation of HbA1c and the further implications it may have on the diagnosis and management of Type 2 diabetes. A literature search was performed using PubMed®/MEDLINE® and Google Scholar with formulated keywords (sickle cell trait, HbAS, HbA1c, glycosylated hemoglobin, diabetes, RBC lifespan, race, and genetics), with the majority of results being mainly observational studies. The National Glycohemoglobin Standardization Program (NGSP) is responsible for standardizing HbA1c results and also highlights factors that can interfere with HbA1c, including hemoglobin variants. Studies that utilize only an NGSP-certified method with no clinically significant interference by HbS in patients with and without SCT showed contrasting results. Additional studies showed that persons of African ancestry, the group to which the majority of SCT patients belong, have a higher HbA1c than non-Hispanic whites (NHWs), just based on race, and a greater probability of having glucose-6-phosphate dehydrogenase (G6PD) deficiency, which lowers HbA1c. The most extensive study investigating the RBC lifespan in SCT patients showed a reduction in the cell lifespan compared to normal patients; however, other smaller studies were contradictory. Our study highlights the need for hemoglobinopathy detection before or during HbA1c measurement in populations with a high degree of African ancestry and the importance of patient notification. It also shows that SCT affects the accuracy of HbA1c, through its likely reduction of RBC lifespan and its increased association with African ancestry and G6PD deficiency. This review recommends that for SCT patients with potential Type 2 diabetes, HbA1c should be used in combination with another diagnostic tool such as fasting blood glucose, fructosamine, or glycated albumin to decrease the chances of a missed diagnosis.
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Affiliation(s)
- Domonick K Gordon
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Scarborough General Hospital, Scarborough, TTO
| | - Madiha Hussain
- Neuropsychiatry, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Prabhat Kumar
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, USA
- Medicine and Surgery, Bangalore Medical College & Research Institute, Bangalore, IND
| | - Sara Khan
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Joung HN, Kwon HS, Baek KH, Song KH, Kim MK. Consistency of the Glycation Gap with the Hemoglobin Glycation Index Derived from a Continuous Glucose Monitoring System. Endocrinol Metab (Seoul) 2020; 35:377-383. [PMID: 32615722 PMCID: PMC7386126 DOI: 10.3803/enm.2020.35.2.377] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 04/23/2020] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Discordances between glycated hemoglobin (HbA1c) levels and glycemic control are common in clinical practice. We aimed to investigate the consistency of the glycation gap with the hemoglobin glycation index (HGI). METHODS From 2016 to 2019, 36 patients with type 2 diabetes were enrolled. HbA1c, glycated albumin (GA), and fasting blood glucose levels were simultaneously measured and 72-hour continuous glucose monitoring (CGM) was performed on the same day. Repeated tests were performed at baseline and 1 month later, without changing patients' diabetes management. The HGI was calculated as the difference between the measured HbA1c and the predicted HbA1c that was derived from CGM. The glycation gap was calculated as the difference between the measured and GA-based predicted HbA1c levels. RESULTS Strong correlations were found between the mean blood glucose (MBG)-based HGI and the prebreakfast glucose-based HGI (r=0.867, P<0.001) and between the glycation gap and the MBG-based HGI (r=0.810, P<0.001). A close correlation was found between the MBG-based HGI at baseline and that after 1 month (r=0.729, P<0.001), with a y-intercept of 0 and a positive slope. CONCLUSION The HGI and glycation gap were highly reproducible, and the magnitudes of repeated determinations were closely correlated. Patients with similar mean glucose levels may have significantly different HbA1c levels.
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Affiliation(s)
- Han Na Joung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ki-Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ki-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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32
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Hsia DS, Rasouli N, Pittas AG, Lary CW, Peters A, Lewis MR, Kashyap SR, Johnson KC, LeBlanc ES, Phillips LS, Hempe JM, Desouza CV. Implications of the Hemoglobin Glycation Index on the Diagnosis of Prediabetes and Diabetes. J Clin Endocrinol Metab 2020; 105:5713508. [PMID: 31965161 PMCID: PMC7015453 DOI: 10.1210/clinem/dgaa029] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 01/16/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) from a 75-g oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) can lead to different results when diagnosing prediabetes and diabetes. The Hemoglobin Glycation Index (HGI) quantifies the interindividual variation in glycation resulting in discrepancies between FPG and HbA1c. We used data from the Vitamin D and Type 2 Diabetes (D2d) study to calculate HGI, to identify HGI-associated variables, and to determine how HGI affects prediabetes and diabetes diagnosis. MEASUREMENTS A linear regression equation [HbA1c (%) = 0.0164 × FPG (mg/dL) + 4.2] was derived using the screening cohort (n = 6829) and applied to calculate predicted HbA1c. This was subtracted from the observed HbA1c to determine HGI in the baseline cohort with 2hPG data (n = 3945). Baseline variables plus prediabetes and diabetes diagnosis by FPG, HbA1c, and 2hPG were compared among low, moderate, and high HGI subgroups. RESULTS The proportion of women and Black/African American individuals increased from low to high HGI subgroups. Mean FPG decreased and mean HbA1c increased from low to high HGI subgroups, consistent with the HGI calculation; however, mean 2hPG was not significantly different among HGI subgroups. CONCLUSIONS High HGI was associated with Black race and female sex as reported previously. The observation that 2hPG was not different across HGI subgroups suggests that variation in postprandial glucose is not a significant source of population variation in HGI. Exclusive use of HbA1c for diagnosis will classify more Black individuals and women as having prediabetes compared with using FPG or 2hPG.
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Affiliation(s)
- Daniel S Hsia
- Pennington Biomedical Research Center, Baton Rouge, Louisiana
| | - Neda Rasouli
- University of Colorado, School of Medicine and VA Eastern Colorado Health Care System, Aurora, Colorado
| | - Anastassios G Pittas
- Tufts Medical Center, Boston, Massachusetts
- Correspondence and Reprint Requests: Anastassios Pittas, MD, Tufts Medical Center, 800 Washington Street, Box #268, Boston, Massachusetts 02111.
| | - Christine W Lary
- Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, Maine
| | - Anne Peters
- Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Michael R Lewis
- Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont
| | | | - Karen C Johnson
- University of Tennessee Health Science Center, Memphis, Tennessee
| | - Erin S LeBlanc
- Kaiser Permanente Center for Health Research NW, Portland, Oregon
| | - Lawrence S Phillips
- Atlanta VA Medical Center, Decatur, Georgia and Emory University School of Medicine, Atlanta, Georgia
| | - James M Hempe
- Louisiana State University Health Sciences Center, New Orleans, Louisiana
| | - Cyrus V Desouza
- Omaha VA Medical Center, University of Nebraska Medical Center, Omaha, Nebraska
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33
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Zhang L, Zhang Q. Glycated Plasma Proteins as More Sensitive Markers for Glycemic Control in Type 1 Diabetes. Proteomics Clin Appl 2020; 14:e1900104. [PMID: 31868294 DOI: 10.1002/prca.201900104] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 11/08/2019] [Indexed: 12/12/2022]
Abstract
PURPOSE Glycated hemoglobin (HbA1c) is used clinically for diagnosis and therapeutic management of diabetes. However, HbA1c reflects average blood glucose level over a long period. The aim of this study is to look for short period, more sensitive protein markers that correlate better with glycemic level. EXPERIMENTAL DESIGN The glycated proteome of human plasma from type 1 diabetic individuals with good and poor (n = 20 each) glycemic control are analyzed using an online two-dimensional proteomics approach. Selected glycated peptides are further validated for their potential as candidate biomarkers using parallel reaction monitoring. RESULTS 305 glycated peptides are quantified and 290 are significantly increased in samples with poor glycemic control. 76 of the 88 selected glycated peptides have receiver operating characteristic area under curve (AUC) values greater than 0.8. Six validated glycated peptides with high AUC show high correlation with HbA1c and have higher fold changes between poor and good glycemic control than HbA1c. The parent proteins have half-lives shorter than HbA1c. CONCLUSIONS AND CLINICAL RELEVANCE Using an advanced proteomics platform for protein glycation analysis, glycated peptides and proteins are identified that are promising as more sensitive, shorter term indicators of glycemic control in diabetic patients than the commonly used HbA1c.
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Affiliation(s)
- Lina Zhang
- Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA.,State Key Laboratory of Food Science & Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, China
| | - Qibin Zhang
- Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, 28081, USA.,Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, 27412, USA
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34
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Mustafa IO, Tanko Y, Yusuf R, Musa SA. The use of glycated haemoglobin (HbA1 C) in determining glycemic control (and relevance of BMI) in diabetic patients in Ahmadu Bello University Teaching Hospital Zaria, Nigeria. Diabetes Metab Syndr 2019; 13:2967-2972. [PMID: 31437811 DOI: 10.1016/j.dsx.2019.07.057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 07/29/2019] [Indexed: 11/20/2022]
Abstract
This study was carried out to specifically investigate the local HbA1C level and determine extent of (if any) variation from the WHO (World Health Organization) recommended threshold for the diagnosis of diabetes and prediabetes using blood glucose as a benchmark. In addition, we also looked to see what role BMI (Body Mass Index) plays among subjects used for the study. 152 subjects were used for the study: 101 diabetic subjects and 51 non-diabetic control subjects. 5 mL of blood sample was collected from each of the subjects after about 8-10 h of overnight fasting. 3-4 mL of the sample was centrifuged and the serum analysed for glucose. The remaining 1-2 ml was transferred into EDTA bottles and analysed immediately for glycated haemoglobin (HbA1C). The BMI (kg/m2) was calculated by dividing the weight in kilograms (kg) by the square of the height in metres (m2). For the BMI, no significant difference was observed between the diabetic subjects (mean = 25.75 kg/m2) and the non-diabetic control subjects (mean = 25.09 kg/m2). Thirty-seven (37) of the diabetic subjects and twenty-three (23) of the non-diabetic subjects had HbA1C levels (mean = 6.96% and 6.29% respectively) that would imply either prediabetes or diabetes but were actually normal going by their fasting blood glucose (FBG) levels. A new chart for the interconversions between FBG and HbA1c and for predicting their expected values from each other was realized, drawn up and recommended for consideration in the management of diabetic patients along with the WHO recommended chart. There are a lot of normal individuals with HbA1c level that does not conform to (or that are simply higher than) what is regarded as the threshold for the onset of diabetes or prediabetes. Generally, the local (Nigerian) glycated haemoglobin (HbA1c) level can therefore be said to be distinctly higher for a given blood glucose range and should be taken as such in the management of diabetes in this environment. Being overweight or obese is not prerequisite to the development of diabetes or abnormal glycated haemoglobin level.
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Affiliation(s)
| | - Yusuf Tanko
- Department of Human Physiology, Ahmadu Bello University, Zaria, Nigeria
| | - Rasheed Yusuf
- Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
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35
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Chalew S, Gomez R. A labile form of hemoglobin A1c is higher in African-American youth with type 1 diabetes compared to Caucasian patients at similar glucose levels. Pediatr Diabetes 2019; 20:736-742. [PMID: 31038272 DOI: 10.1111/pedi.12863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 03/26/2019] [Accepted: 03/28/2019] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Hemoglobin A1c (HbA1c) levels are higher in African-American (AA) individuals compared to Caucasians (EA) even after adjustment for blood glucose levels. To better understand the mechanism of this disparity we examined the relationship of an unstable (labile) form of HbA1c (L-HbA1c) with race and glucose. METHODS Samples for HbA1c were collected from pediatric patients self-identified as either AA (15F, 12M, age 13.4 ± 3.5 years) or EA (22F, 30M, age 14.6 ± 3.4 years) with type 1 diabetes at the time of a clinic visit. Clinic HbA1c (HbA1c) was performed by immunoassay. L-HbA1c equaled the difference in the HbA1c fraction by dynamic capillary isoelectric focusing before and after incubation in a low pH buffer. A capillary glucose (Clinic-BG) was measured at clinic visit. Mean blood glucose (MBG) was calculated from the last 30 days of the patient's glucose meter data. The influence of race on L-HbA1c was assessed in a multiple variable regression model adjusted for Clinic-BG. RESULTS The groups were similar for age and duration of diabetes. L-HbA1c was correlated with Clinic-BG, MBG, and HbA1c. The mean levels of L-HbA1c, HbA1c, MBG, but not Clinic-BG were higher in AA patients compared to EA. After adjustment for Clinic-BG, L-HbA1c was still higher in AA (2.8 ± 0.7% AA vs 2.1 ± 0.7% EA, P < .0001). CONCLUSIONS L-HbA1c is correlated with Clinic-BG. At any given level of Clinic-BG, AA patients have higher levels of L-HbA1c than EA. This preliminary study suggests that early factors prior to the formation of stable HbA1c may contribute to the observed glucose-independent racial disparity.
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Affiliation(s)
- Stuart Chalew
- Division of Pediatric Endocrinology Children's Hospital of New Orleans and LSU Health Sciences Center, Research Institute for Children, New Orleans, Louisiana
| | - Ricardo Gomez
- Division of Pediatric Endocrinology Children's Hospital of New Orleans and LSU Health Sciences Center, Research Institute for Children, New Orleans, Louisiana
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36
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Comparative Abilities of Fasting Plasma Glucose and Haemoglobin A1c in Predicting Metabolic Syndrome among Apparently Healthy Normoglycemic Ghanaian Adults. Int J Chronic Dis 2019; 2019:2578171. [PMID: 31428625 PMCID: PMC6681621 DOI: 10.1155/2019/2578171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 06/01/2019] [Accepted: 07/16/2019] [Indexed: 01/21/2023] Open
Abstract
There are arguments as to whether haemoglobin A1c (HbA1c) better predicts Metabolic syndrome (MetS) than fasting plasma glucose. The aim of the study was to explore the comparative abilities of HbA1c and Fasting plasma glucose (FPG) in predicting cardiometabolic risk among apparently healthy adults in the Tamale metropolis. This study was a cross-sectional study conducted in the Tamale metropolis from September, 2017, to January, 2018, among one hundred and sixty (160) apparently healthy normoglycemic adults. A self-designed questionnaire was administered to gather sociodemographic data. Anthropometric and haemodynamic data were also taken and blood samples collected for haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and lipid profile. MetS was classified using the harmonised criteria as indicated in the joint interim statement (JIS). Out of the 160 participants, 42.5% were males and 57.5% were females. FPG associated better with MetS and other cardiovascular risk markers, compared to HbA1c. FPG had the largest area under curve for predicting MetS and its components. This study shows a stronger association between FPG and MetS compared with haemoglobin A1c; it also provides evidence of a superior ability of FPG over HbA1c in predicting MetS and other adverse cardiovascular outcomes in apparently heathy normoglycemic individuals.
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37
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Nayak AU, Singh BM, Dunmore SJ. Potential Clinical Error Arising From Use of HbA1c in Diabetes: Effects of the Glycation Gap. Endocr Rev 2019; 40:988-999. [PMID: 31074800 DOI: 10.1210/er.2018-00284] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 04/05/2019] [Indexed: 01/17/2023]
Abstract
The glycation gap (GGap) and the similar hemoglobin glycation index (HGI) define consistent differences between glycated hemoglobin and actual glycemia derived from fructosamine or mean blood glucose, respectively. Such a disparity may be found in a substantial proportion of people with diabetes, being >1 U of glycated HbA1c% or 7.2 mmol/mol in almost 40% of estimations. In this review we define these indices and explain how they can be calculated and that they are not spurious, being consistent in individuals over time. We evaluate the evidence that GGap and HGI are associated with variation in risk of complications and mortality and demonstrate the potential for clinical error in the unquestioning use of HbA1c. We explore the underlying etiology of the variation of HbA1c from mean glucose in blood plasma, including the potential role of enzymatic deglycation of hemoglobin by fructosamine-3-kinase. We conclude that measurement of GGap and HGI are important to diabetes clinicians and their patients in individualization of therapy and the avoidance of harm arising from consequent inappropriate assessment of glycemia and use of therapies.
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Affiliation(s)
- Ananth U Nayak
- Department of Endocrinology and Diabetes, University Hospital of North Midlands NHS Trust, Stoke on Trent, United Kingdom
| | - Baldev M Singh
- Diabetes Research Group, School of Medicine and Clinical Practice, University of Wolverhampton, Wolverhampton, United Kingdom.,Wolverhampton Diabetes Centre, New Cross Hospital, Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
| | - Simon J Dunmore
- Diabetes Research Group, School of Medicine and Clinical Practice, University of Wolverhampton, Wolverhampton, United Kingdom
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Wang X, Su J, Zeng D, Liu G, Liu L, Xu Y, Wang C, Liu X, Wang L, Mi X. Gold nano-flowers (Au NFs) modified screen-printed carbon electrode electrochemical biosensor for label-free and quantitative detection of glycated hemoglobin. Talanta 2019; 201:119-125. [PMID: 31122401 DOI: 10.1016/j.talanta.2019.03.100] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 03/14/2019] [Accepted: 03/30/2019] [Indexed: 01/18/2023]
Abstract
Glycated hemoglobin (HbA1c) represents the average glucose level over the past three months and has been considered as the most important biomarker for the diagnosis of Type Ⅱ diabetes (T2D). Herein, a label-free and quantitative electrochemical biosensor based on 4-mercaptophenylboronic acid (4-MPBA) modified gold nano-flowers (Au NFs) substrate was developed for the determination of HbA1c. Under optimal conditions, the linear dynamic ranges of HbA1c (5 μg/mL - 1000 μg/mL) and HbA1c% (2%-20%) by cyclic voltammetry were achieved. The electrochemical biosensor showed great detection specificity towards HbA1c and relatively stability after storage at 4 °C. This method could also be applied in human serum system which holds great potential to be applied to monitor real blood samples of diabetes patients. In human serum system, the recovery rate could reach 103.8% and 99.0%. It could achieve fast detection, the total analysis time was less than 65 min, and the detection time was less than 10 s. Moreover, in terms of fabrication process, operation procedure, detection time and cost, this technique was superior to the current HbA1c detection methods suggesting great promise for the practical clinical use in the future.
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Affiliation(s)
- Xiao Wang
- , School of Life Sciences, Shanghai University, Shanghai, 200444, China; , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Jing Su
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Dongdong Zeng
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Gang Liu
- , Division of Chemistry and Ionizing Radiation Measurement Technology, Shanghai Institute of Measurement and Testing Technology, Shanghai, 201203, China
| | - Lizhuang Liu
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Yi Xu
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Chenguang Wang
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Xinxin Liu
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Lu Wang
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Xianqiang Mi
- , Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China; , State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
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Krhač M, Lovrenčić MV. Update on biomarkers of glycemic control. World J Diabetes 2019; 10:1-15. [PMID: 30697366 PMCID: PMC6347654 DOI: 10.4239/wjd.v10.i1.1] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 11/14/2018] [Accepted: 12/05/2018] [Indexed: 02/05/2023] Open
Abstract
Attaining and maintaining good glycemic control is a cornerstone of diabetes care. The monitoring of glycemic control is currently based on the self-monitoring of blood glucose (SMBG) and laboratory testing for hemoglobin A1c (HbA1c), which is a surrogate biochemical marker of the average glycemia level over the previous 2-3 mo period. Although hyperglycemia is a key biochemical feature of diabetes, both the level of and exposure to high glucose, as well as glycemic variability, contribute to the pathogenesis of diabetic complications and follow different patterns in type 1 and type 2 diabetes. HbA1c provides a valuable, standardized and evidence-based parameter that is relevant for clinical decision making, but several biological and analytical confounders limit its accuracy in reflecting true glycemia. It has become apparent in recent years that other glycated proteins such as fructosamine, glycated albumin, and the nutritional monosaccharide 1,5-anhydroglucitol, as well as integrated measures from direct glucose testing by an SMBG/continuous glucose monitoring system, may provide valuable complementary data, particularly in circumstances when HbA1c results may be unreliable or are insufficient to assess the risk of adverse outcomes. Long-term associations of these alternative biomarkers of glycemia with the risk of complications need to be investigated in order to provide clinically relevant cut-off values and to validate their utility in diverse populations of diabetes patients.
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Affiliation(s)
- Maja Krhač
- Division of Laboratory Medicine, Department of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, Zagreb 10000, Croatia
| | - Marijana Vučić Lovrenčić
- Division of Laboratory Medicine, Department of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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Chalew S, Hamdan M. Racial disparity in HbA1c persists when fructosamine is used as a surrogate for mean blood glucose in youth with type 1 diabetes. Pediatr Diabetes 2018; 19:1243-1248. [PMID: 29808574 PMCID: PMC6925540 DOI: 10.1111/pedi.12696] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Revised: 04/13/2018] [Accepted: 05/16/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Blacks have been reported to have higher hemoglobin A1c (HbA1c) than Whites even after adjustment for differences in blood glucose levels. Potentially glucose-independent racial disparity in HbA1c is an artifact of glucose ascertainment methods. In order to test this possibility, we examined the relationship of HbA1c with race after adjustment for concurrent fructosamine level as a surrogate for mean blood glucose (MBG). METHODS Youth with type 1 diabetes self-identified as either Black or White had blood drawn for HbA1c, fructosamine complete blood count, ferritin, and soluble transferrin receptor (sTfR) at a clinic visit. MBG was calculated as the average of self-monitored capillary glucoses over the preceding 30 days. The effect of race on HbA1c was evaluated in a general linear model adjusting for either MBG or fructosamine, along with other covariates. RESULTS Fructosamine was correlated with both HbA1c (r = 0.73, P < .0001), MBG (r = 0.46, P < .0001), red cell distribution width coefficient of variation (RDW-CV) (r = 0.31, P = .0045), Fe (r = 0.27, P = .017), and sTfR (r = 0.32, P = .0042). HbA1c was approximately 0.7% higher in Blacks than Whites after adjustment for fructosamine along with age, gender, RDW-CV, Fe, sTfR. CONCLUSIONS Blacks tend to have higher HbA1c than Whites even after statistical adjustment for fructosamine levels as a surrogate for MBG. Thus, HbA1c tends to overestimate corresponding MBG or fructosamine levels in Black patients. Racial differences should be taken into consideration when using HbA1c as a guide to diagnosis and therapy of diabetes in mixed-race populations.
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Affiliation(s)
- Stuart Chalew
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics; Louisiana State University Health Science Center, Children's Hospital of New Orleans; New Orleans Louisiana
| | - Mahmoud Hamdan
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics; Louisiana State University Health Science Center, Children's Hospital of New Orleans; New Orleans Louisiana
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Kim MK, Jeong JS, Yun JS, Kwon HS, Baek KH, Song KH, Ahn YB, Ko SH. Hemoglobin glycation index predicts cardiovascular disease in people with type 2 diabetes mellitus: A 10-year longitudinal cohort study. J Diabetes Complications 2018; 32:906-910. [PMID: 30121206 DOI: 10.1016/j.jdiacomp.2018.08.007] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 08/03/2018] [Accepted: 08/06/2018] [Indexed: 01/09/2023]
Abstract
BACKGROUND AND AIMS Previous studies have suggested that the hemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications. We examined the prognostic significance of a high HGI for cardiovascular disease (CVD) in an ongoing hospital-based cohort. METHODS From March 2003 to December 2004, 1302 consecutive patients with type 2 diabetes and without a prior history of CVD were enrolled. CVD was defined as the occurrence of coronary artery disease or ischemic stroke. The HGI was calculated as the measured glycated hemoglobin (HbA1c) minus predicted HbA1c. Predicted HbA1c were calculated for 1302 participants by inserting fasting blood glucose (FBG) into the equation, Predicted HbA1c level = 0.02106 × FBG [mg/dL] + 4.973. Cox proportional hazards models were used to identify the associations between the HGI and CVD after adjusting for confounding variables. RESULTS During 11.1 years of follow-up, 225 participants (17.2%) were newly diagnosed with CVD. The baseline HGI was significantly higher in subjects with incident CVD than in those without CVD, although the baseline FBG levels did not differ according to the occurrence of CVD. Compared with patients without CVD, those with CVD were older, had a longer duration of diabetes and hypertension, and used more insulin at baseline. A Cox hazard regression analysis revealed that the development of CVD was significantly associated with baseline HGI (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.31-2.87; p < 0.001, comparing the highest and lowest quartiles of HGI). This relationship was unchanged after additional adjustment for baseline HbA1c level (HR, 1.74; 95% CI, 1.08-2.81). The HRs of HbA1c in relation to outcomes were similar to or lower than those seen for HGI. After adjustment for HGI, the effect of the highest HbA1c on incident CVD disappeared. CONCLUSIONS High HGI was independently associated with incident CVD in patients with type 2 diabetes. Patients with high HGI at baseline had a higher inherent risk for CVD.
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Affiliation(s)
- Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jee Sun Jeong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae-Seung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yu-Bae Ahn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Distribution of glycated haemoglobin and its determinants in Korean youth and young adults: a nationwide population-based study. Sci Rep 2018; 8:1962. [PMID: 29386645 PMCID: PMC5792600 DOI: 10.1038/s41598-018-20274-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Accepted: 01/16/2018] [Indexed: 12/18/2022] Open
Abstract
The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10–19 years old) and young adults (20–29 years old). Data from the Korea Health and Nutrition Examination Survey (2011–2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10–29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P < 0.001). Male participants showed significantly higher HbA1c level than females (P < 0.001). When age was grouped into 5-year intervals, HbA1c was the highest in those aged 10–14 years and the lowest in those aged 20–24 years. After controlling for confounding variables, the HbA1c values of youths and male participants were significantly higher than those of young adults and female participants. The present study provides nationally representative data on the distribution of HbA1c values in Korean youth and young adults. There were significant differences in the level of HbA1c according to age and sex.
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Kim MK, Jeong JS, Kwon HS, Baek KH, Song KH. Concordance the hemoglobin glycation index with glycation gap using glycated albumin in patients with type 2 diabetes. J Diabetes Complications 2017; 31:1127-1131. [PMID: 28487124 DOI: 10.1016/j.jdiacomp.2017.04.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 03/24/2017] [Accepted: 04/12/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The hemoglobin glycation index (HGI) is an index of differences in the glycation of hemoglobin according to blood glucose level. The glycation gap (G-gap) is an empiric measure of the extent of disagreement between hemoglobin A1C (HbA1C) and glycated albumin (GA). The aim of this study was to investigate the extent of agreement between the HGI and G-gap with respect to GA level, and to elucidate factors related to a high HGI. METHOD Data were obtained from 105 patients with type 2 diabetes, and fasting blood glucose (FBG), HbA1c, and GA values were measured simultaneously. The G-gap was calculated as the difference between the measured and GA-based predicted HbA1c levels. HGI was calculated as the difference between measured and FBG-based predicted HbA1c levels. RESULTS The HGI and G-gap were highly correlated according GA (r=0.722, P<0.001). In general, the two indices were similar in terms of both direction and magnitude. The classification of patients as high, moderate, or low glycators based on HGI versus G-gap was consistent for the majority of the population and only 5% of patients were reclassified from high to low or low to high. Fasting C-peptide levels decreased linearly, and the percentage of patients using insulin increased linearly, between the lowest and highest HGI tertile (both P<0.05). CONCLUSIONS There was 95% agreement between the HGI and G-gap using GA among type 2 diabetes patients. Furthermore, a high HGI was associated with a higher prevalence of insulin use among type 2 diabetes patients.
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Affiliation(s)
- Mee Kyoung Kim
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jee Sun Jeong
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyuk-Sang Kwon
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Hyun Baek
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Ho Song
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Wright LAC, Hirsch IB. Metrics Beyond Hemoglobin A1C in Diabetes Management: Time in Range, Hypoglycemia, and Other Parameters. Diabetes Technol Ther 2017; 19:S16-S26. [PMID: 28541136 PMCID: PMC5444503 DOI: 10.1089/dia.2017.0029] [Citation(s) in RCA: 124] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
We review clinical instances in which A1C should not be used and reflect on the use of other glucose metrics that can be used, in substitution of or in combination with A1C and SMBG, to tailor an individualized approach that will result in better outcomes and patient empowerment.
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Affiliation(s)
- Lorena Alarcon-Casas Wright
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington Medical Center/Roosevelt , Seattle, Washington
| | - Irl B Hirsch
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington Medical Center/Roosevelt , Seattle, Washington
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Garla V, Yanes-Cardozo L, Lien LF. Current therapeutic approaches in the management of hyperglycemia in chronic renal disease. Rev Endocr Metab Disord 2017; 18:5-19. [PMID: 28258533 DOI: 10.1007/s11154-017-9416-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD. With regard to medication management in the care of patients with DM, CKD has significant effects. For example, the dosages of oral and non-insulin anti-hyperglycemic agents often need to be modified according to renal function. Insulin metabolism is altered in CKD, and a reduction in insulin dose is almost always needed. Dialysis also affects various aspects of glucose homeostasis, necessitating appropriate changes in therapy. Due to the aforementioned factors glycemic management in patients with DM and CKD can be quiet challenging.
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Affiliation(s)
- Vishnu Garla
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
| | - Licy Yanes-Cardozo
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA
| | - Lillian F Lien
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA
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Cavagnolli G, Pimentel AL, Freitas PAC, Gross JL, Camargo JL. Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis. PLoS One 2017; 12:e0171315. [PMID: 28192447 PMCID: PMC5305058 DOI: 10.1371/journal.pone.0171315] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 01/18/2017] [Indexed: 12/16/2022] Open
Abstract
Aims/Hypothesis Disparities in HbA1c levels have been observed among ethnic groups. Most studies were performed in patients with diabetes mellitus (DM), which may interfere with results due to the high variability of glucose levels. We conducted a systematic review and meta-analysis to investigate the effect of ethnicity on HbA1c levels in individuals without DM. Methods This is a systematic review with meta-analysis. We searched MEDLINE and EMBASE up to September 2016. Studies published after 1996, performed in adults without DM, reporting HbA1c results measured by certified/standardized methods were included. A random effects model was used and the effect size was presented as weighted HbA1c mean difference (95% CI) between different ethnicities as compared to White ethnicity. Results Twelve studies met the inclusion criteria, totalling data from 49,238 individuals. There were significant differences between HbA1c levels in Blacks [0.26% (2.8 mmol/mol); 95% CI 0.18 to 0.33 (2.0 to 3.6), p <0.001; I2 = 90%, p <0.001], Asians [0.24% (2.6 mmol/mol); 95% CI 0.16 to 0.33 (1.7 to 3.6), p <0.001; I2 = 80%, p = 0.0006] and Latinos [0.08% (0.9 mmol/mol); IC 95% 0.06 to 0.10 (0.7 to 1.1); p <0.001; I2 = 0%; p = 0.72] when compared to Whites. Conclusions/Interpretation This meta-analysis shows that, in individuals without DM, HbA1c values are higher in Blacks, Asians, and Latinos when compared to White persons. Although small, these differences might have impact on the use of a sole HbA1c point to diagnose DM in all ethnic populations.
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Affiliation(s)
- Gabriela Cavagnolli
- Graduate Program in Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Centro Universitário FSG, Caxias do Sul, Brazil
| | - Ana Laura Pimentel
- Graduate Program in Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Priscila Aparecida Correa Freitas
- Graduate Program in Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Laboratory of Transplantation Immunology, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil
| | - Jorge Luiz Gross
- Graduate Program in Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Joíza Lins Camargo
- Graduate Program in Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- * E-mail:
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Jaramillo R, Shuck SC, Chan YS, Liu X, Bates SE, Lim PP, Tamae D, Lacoste S, O'Connor TR, Termini J. DNA Advanced Glycation End Products (DNA-AGEs) Are Elevated in Urine and Tissue in an Animal Model of Type 2 Diabetes. Chem Res Toxicol 2017; 30:689-698. [PMID: 28107623 DOI: 10.1021/acs.chemrestox.6b00414] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
More precise identification and treatment monitoring of prediabetic/diabetic individuals will require additional biomarkers to complement existing diagnostic tests. Candidates include hyperglycemia-induced adducts such as advanced glycation end products (AGEs) of proteins, lipids, and DNA. The potential for DNA-AGEs as diabetic biomarkers was examined in a longitudinal study using the Leprdb/db animal model of metabolic syndrome. The DNA-AGE, N2-(1-carboxyethyl)-2'-deoxyguanosine (CEdG) was quantified by mass spectrometry using isotope dilution from the urine and tissue of hyperglycemic and normoglycemic mice. Hyperglycemic mice (fasting plasma glucose, FPG, ≥ 200 mg/dL) displayed a higher median urinary CEdG value (238.4 ± 112.8 pmol/24 h) than normoglycemic mice (16.1 ± 11.8 pmol/24 h). Logistic regression analysis revealed urinary CEdG to be an independent predictor of hyperglycemia. Urinary CEdG was positively correlated with FPG in hyperglycemic animals and with HbA1c for all mice. Average tissue-derived CEdG was also higher in hyperglycemic mice (18.4 CEdG/106 dG) than normoglycemic mice (4.4 CEdG/106 dG). Urinary CEdG was significantly elevated in Leprdb/db mice relative to Leprwt/wt, and tissue CEdG values increased in the order Leprwt/wt < Leprwt/db < Leprdb/db. These data suggest that urinary CEdG measurement may provide a noninvasive quantitative index of glycemic status and augment existing biomarkers for the diagnosis and monitoring of diabetes.
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Affiliation(s)
- Richard Jaramillo
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Sarah C Shuck
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Yin S Chan
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Xueli Liu
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Steven E Bates
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Punnajit P Lim
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Daniel Tamae
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Sandrine Lacoste
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - Timothy R O'Connor
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
| | - John Termini
- Departments of Molecular Medicine, ‡Biostatistics, and §Cancer Biology, Beckman Research Institute at City of Hope , Duarte, California 91010, United States
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Cohen RM, Franco RS. Can Red Blood Cell Indices Act as Surrogate Markers for Discordance between Hemoglobin A1c and Fasting Blood Glucose? Clin Chem 2016; 62:1551-1553. [PMID: 27694390 DOI: 10.1373/clinchem.2016.264705] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 09/13/2016] [Indexed: 01/31/2023]
Affiliation(s)
- Robert M Cohen
- Cincinnati Veterans Affairs Medical Center, Cincinnati, OH; .,Divisions of Endocrinology and
| | - Robert S Franco
- Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH
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Hamdan MAA, Hempe JM, Velasco-Gonzalez C, Gomez R, Vargas A, Chalew S. Differences in Red Blood Cell Indices Do Not Explain Racial Disparity in Hemoglobin A1c in Children with Type 1 Diabetes. J Pediatr 2016; 176:197-9. [PMID: 27156184 PMCID: PMC5432208 DOI: 10.1016/j.jpeds.2016.03.068] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Revised: 03/03/2016] [Accepted: 03/25/2016] [Indexed: 01/16/2023]
Abstract
We assessed the association of erythrocyte indices on mean blood glucose-independent racial disparity in hemoglobin A1c (HbA1c) in youth with type 1 diabetes. Blacks still had higher HbA1c after adjustment for mean blood glucose, red blood cell indices, age, and sex. Such differences need to be taken into account when interpreting HbA1c in Black patients.
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Affiliation(s)
- Mahmoud Adeeb Ahmad Hamdan
- Pediatric Endocrinology, Children's Hospital of New Orleans, New Orleans, LA; Louisiana State University Health Science Center, New Orleans, LA
| | - James M Hempe
- Louisiana State University Health Science Center, New Orleans, LA; Research Institute for Children, Children's Hospital of New Orleans, New Orleans, LA
| | | | - Ricardo Gomez
- Pediatric Endocrinology, Children's Hospital of New Orleans, New Orleans, LA; Louisiana State University Health Science Center, New Orleans, LA
| | - Alfonso Vargas
- Pediatric Endocrinology, Children's Hospital of New Orleans, New Orleans, LA; Louisiana State University Health Science Center, New Orleans, LA
| | - Stuart Chalew
- Pediatric Endocrinology, Children's Hospital of New Orleans, New Orleans, LA; Louisiana State University Health Science Center, New Orleans, LA; Research Institute for Children, Children's Hospital of New Orleans, New Orleans, LA.
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Herpol M, Lanckmans K, Van Neyghem S, Clement P, Crevits S, De Crem K, Gorus FK, Weets I. Evaluation of the Sebia Capillarys 3 Tera and the Bio-Rad D-100 Systems for the Measurement of Hemoglobin A1c. Am J Clin Pathol 2016; 146:67-77. [PMID: 27357293 DOI: 10.1093/ajcp/aqw081] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES We evaluated the Bio-Rad (Irvine, CA) D-100 and the Sebia (Lisses, France) Capillarys 3 Tera for the measurement of hemoglobin A1c (HbA1c) in venous blood samples. METHODS Whole-blood samples and control material were analyzed with the D-100 and Capillarys 3 Tera and compared with our routine method, HLC-723G7 (Tosoh, Tokyo, Japan). An evaluation protocol to test precision, trueness, linearity, carryover, and selectivity was set up according to Clinical and Laboratory Standards Institute guidelines. The results were presented in National Glycohemoglobin Standardization Program and International Federation of Clinical Chemistry (IFCC) units. RESULTS Both systems showed excellent precision (total coefficients of variation <2%, IFCC) and bias (<0.3% or 3 mmol/mol). Linearity was demonstrated for HbA1c values from 3.8% (18 mmol/mol) to 18.5% (179 mmol/mol). Results were correlated with the routine method using Bland-Altman analysis, showing a mean difference of 0.33% or 3.6 mmol/mol for the D-100 and of 0.25% or 2.6 mmol/mol for the Capillarys 3 Tera vs HLC-723G7. None of the automated instruments were prone to interferences by labile HbA1c (≤10 g/L glucose), carbamylated hemoglobin (≤0.5 mmol/L potassium cyanate), hemoglobin variants, bilirubin (≤15 mg/dL), and triglycerides (≤3,360 mg/dL). CONCLUSIONS The Bio-Rad D-100 and the Sebia Capillarys 3 Tera instruments performed well for the determination of HbA1c in terms of quality criteria as well as for sample throughput.
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Affiliation(s)
- Margaux Herpol
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Katrien Lanckmans
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Stefaan Van Neyghem
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Pascale Clement
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Stefanie Crevits
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Kim De Crem
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Frans K Gorus
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Ilse Weets
- From the Department of Clinical Chemistry and Radio-Immunology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
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