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Association of glycated albumin to hemoglobin A1c ratio with all-cause and cardiovascular mortality among US adults: A population-based cohort study

  • Author Footnotes
    1 S. Wang and L. Gu contributed equally to this work.
    Sibo Wang
    Footnotes
    1 S. Wang and L. Gu contributed equally to this work.
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
    Search for articles by this author
  • Author Footnotes
    1 S. Wang and L. Gu contributed equally to this work.
    Lingfeng Gu
    Footnotes
    1 S. Wang and L. Gu contributed equally to this work.
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
    Search for articles by this author
  • Jun Zhu
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China

    Department of Cardiology, Geriatrics Hospital of Jiangsu Province, Nanjing 210024, China
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  • Tiankai Shan
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
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  • Jiateng Sun
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
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  • Qiqi Jiang
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
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  • Hao Wang
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
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  • Di Zhao
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
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  • Qiming Wang
    Correspondence
    Corresponding authors at: Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, 300 Guangzhou Road, Nanjing 210029, China.
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
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  • Liansheng Wang
    Correspondence
    Corresponding authors at: Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, 300 Guangzhou Road, Nanjing 210029, China.
    Affiliations
    Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China
    Search for articles by this author
  • Author Footnotes
    1 S. Wang and L. Gu contributed equally to this work.
Published:October 11, 2022DOI:https://doi.org/10.1016/j.diabres.2022.110116

      Abstract

      Aims

      To investigate the association of glycated albumin to hemoglobin A1c (GA/HbA1c) ratio, an indicator of blood glucose fluctuations, with all-cause and cardiovascular mortality among US adults.

      Methods

      This cohort study used data from the National Health and Nutrition Examination Survey 1999–2004. Participants were linked to National Death Index mortality data through December 31, 2015. Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and restricted cubic spline (RCS) regression was conducted.

      Results

      A total of 11,508 US adults (weighted mean age, 43.9 years; 5748 males [weighted, 48.9 %]) were included. During a median follow‑up of 13.6 years, 1963 total deaths occurred, including 383 cardiovascular deaths. After multivariable adjustments, a higher GA/HbA1c ratio was associated with a higher risk of all-cause (tertiles: P for trend < 0.001; continuous: HR 1.49 [95 % CI 1.32–1.69]) and cardiovascular (tertiles: P for trend = 0.048; continuous: HR 1.65 [95 % CI 1.27–2.14]) mortality. RCS revealed a linear relationship of GA/HbA1c ratio to mortality.

      Conclusions

      In the nationally representative cohort of US adults, GA/HbA1c ratio was significantly associated with the risk of all-cause and cardiovascular mortality. These findings suggest that GA/HbA1c ratio may serve as an effective indicator for identifying high-risk individuals.

      Keywords

      Abbreviations:

      AGEs (advanced glycation end products), BMI (body mass index), CI (confidence interval), CRP (C-reactive protein), CVD (cardiovascular disease), eGFR (estimated glomerular filtration rate), GA (glycated albumin), GA/HbA1c ratio (glycated albumin to hemoglobin A1c ratio), HbA1c (hemoglobin A1c), HDL-C (high-density lipoprotein cholesterol), HR (hazard ratio), LDL-C (low-density lipoprotein cholesterol), NHANES (National Health and Nutrition Examination Survey), RCS (restricted cubic spline), T1D (type 1 diabetes), T2D (type 2 diabetes)
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      References

        • Katsarou A.
        • Gudbjörnsdottir S.
        • Rawshani A.
        • Dabelea D.
        • Bonifacio E.
        • Anderson B.J.
        • et al.
        Type 1 diabetes mellitus.
        Nat Rev Dis Primers. 2017; 3https://doi.org/10.1038/nrdp.2017.16
        • DeFronzo R.A.
        • Ferrannini E.
        • Groop L.
        • Henry R.R.
        • Herman W.H.
        • Holst J.J.
        • et al.
        Type 2 diabetes mellitus.
        Nat Rev Dis Primers. 2015; 1https://doi.org/10.1038/nrdp.2015.19
        • Vos T.
        • Lim S.S.
        • Abbafati C.
        • Abbas K.M.
        • Abbasi M.
        • Abbasifard M.
        • et al.
        Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019.
        Lancet. 2020; 396: 1204-1222
      1. American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022;45(Suppl 1):S17–S38. doi: 10.2337/dc22-S002.

        • Yazdanpanah S.
        • Rabiee M.
        • Tahriri M.
        • Abdolrahim M.
        • Rajab A.
        • Jazayeri H.E.
        • et al.
        Evaluation of glycated albumin (GA) and GA/HbA1c ratio for diagnosis of diabetes and glycemic control: a comprehensive review.
        Crit Rev Clin Lab Sci. 2017; 54: 219-232
      2. Nusca A, Tuccinardi D, Albano M, Cavallaro C, Ricottini E, Manfrini S, et al. Glycemic variability in the development of cardiovascular complications in diabetes. Diabetes Metab Res Rev. 2018;34(8):e3047. doi: 10.1002/dmrr.3047.

        • Yamamoto H.
        • Shinke T.
        • Otake H.
        • Kawamori H.
        • Toba T.
        • Kuroda M.
        • et al.
        Impact of daily glucose fluctuations on cardiovascular outcomes after percutaneous coronary intervention for patients with stable coronary artery disease undergoing lipid-lowering therapy.
        J Diabetes Investig. 2021; 12: 1015-1024
        • Hoshino J.
        • Hamano T.
        • Abe M.
        • Hasegawa T.
        • Wada A.
        • Ubara Y.
        • et al.
        Glycated albumin versus hemoglobin A1c and mortality in diabetic hemodialysis patients: a cohort study.
        Nephrol Dial Transplant. 2018; 33: 1150-1158
        • Yoon H.-J.
        • Lee Y.-h.
        • Kim S.R.
        • Rim T.H.
        • Lee E.Y.
        • Kang E.S.
        • et al.
        Glycated albumin and the risk of micro- and macrovascular complications in subjects with type 1 diabetes.
        Cardiovasc Diabetol. 2015; 14https://doi.org/10.1186/s12933-015-0219-y
        • Matsumoto H.
        • Murase-Mishiba Y.
        • Yamamoto N.
        • Sugitatsu-Nakatsukasa S.
        • Shibasaki S.
        • Sano H.
        • et al.
        Glycated albumin to glycated hemoglobin ratio is a sensitive indicator of blood glucose variability in patients with fulminant type 1 diabetes.
        Intern Med. 2012; 51: 1315-1321
      3. Ogawa A, Hayashi A, Kishihara E, Yoshino S, Takeuchi A, Shichiri M. New indices for predicting glycaemic variability. PLoS One. 2012;7(9):e46517. doi: 10.1371/journal.pone.0046517.

        • Wang B.R.
        • Yao J.T.
        • Zheng H.
        • Li Q.M.
        Association of glycated albumin/glycosylated hemoglobin ratio with blood glucose fluctuation and long-term blood glucose control in patients with type 2 diabetes mellitus.
        Diabetes Metab Syndr Obes. 2021; 14: 1809-1815https://doi.org/10.2147/DMSO.S297730
        • Saisho Y.
        • Tanaka K.
        • Abe T.
        • Kawai T.
        • Itoh H.
        Lower beta cell function relates to sustained higher glycated albumin to glycated hemoglobin ratio in Japanese patients with type 2 diabetes.
        Endocr J. 2014; 61: 149-157https://doi.org/10.1507/endocrj.ej13-0376
        • Song S.O.
        • Kim K.J.
        • Lee B.W.
        • Kang E.S.
        • Cha B.S.
        • Lee H.C.
        Serum glycated albumin predicts the progression of carotid arterial atherosclerosis.
        Atherosclerosis. 2012; 225: 450-455https://doi.org/10.1016/j.atherosclerosis.2012.09.005
        • Bao W.
        • Liu B.
        • Rong S.
        • Dai S.Y.
        • Trasande L.
        • Lehmler H.J.
        Association between bisphenol A exposure and risk of all-cause and cause-specific mortality in US adults.
        JAMA Netw Open. 2020; 3: e2011620https://doi.org/10.1001/jamanetworkopen.2020.11620
        • Rooney M.R.
        • Daya N.
        • Tang O.
        • McEvoy J.W.
        • Coresh J.
        • Christenson R.H.
        • et al.
        Glycated albumin and risk of mortality in the US adult population.
        Clin Chem. 2022; 68: 422-430
        • Zhang Y.u.
        • Huang M.
        • Zhuang P.
        • Jiao J.
        • Chen X.
        • Wang J.
        • et al.
        Exposure to acrylamide and the risk of cardiovascular diseases in the National Health and Nutrition Examination Survey 2003–2006.
        Environ Int. 2018; 117: 154-163
        • Kohzuma T.
        • Yamamoto T.
        • Uematsu Y.
        • Shihabi Z.K.
        • Freedman B.I.
        Basic performance of an enzymatic method for glycated albumin and reference range determination.
        J Diabetes Sci Technol. 2011; 5: 1455-1462https://doi.org/10.1177/193229681100500619
        • Xu C.
        • Weng Z.
        • Zhang L.
        • Xu J.
        • Dahal M.
        • Basnet T.B.
        • et al.
        HDL cholesterol: A potential mediator of the association between urinary cadmium concentration and cardiovascular disease risk.
        Ecotoxicol Environ Saf. 2021; 208: 111433
        • Williams B.
        • Mancia G.
        • Spiering W.
        • Agabiti Rosei E.
        • Azizi M.
        • Burnier M.
        • et al.
        2018 ESC/ESH Guidelines for the management of arterial hypertension.
        Eur Heart J. 2018; 39: 3021-3104
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • Zhang Y.(.
        • Castro A.F.
        • Feldman H.I.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604
        • Inoue K.
        • Ritz B.
        • Brent G.A.
        • Ebrahimi R.
        • Rhee C.M.
        • Leung A.M.
        Association of subclinical hypothyroidism and cardiovascular disease with mortality.
        JAMA Netw Open. 2020; 3: e1920745https://doi.org/10.1001/jamanetworkopen.2019.20745
        • Shan Z.
        • Guo Y.
        • Hu F.B.
        • Liu L.
        • Qi Q.
        Association of low-carbohydrate and low-fat diets with mortality among US adults.
        JAMA Intern Med. 2020; 180: 513-523https://doi.org/10.1001/jamainternmed.2019.6980
      4. Johnson CL, Paulose-Ram R, Ogden CL, Carroll MD, Kruszon-Moran D, Dohrmann SM, et al. National health and nutrition examination survey: analytic guidelines, 1999-2010. Vital Health Stat 2. 2013(161):1–24.

        • Zhang Z.
        Multiple imputation with multivariate imputation by chained equation (MICE) package.
        Ann Transl Med. 2016; 4: 30https://doi.org/10.3978/j.issn.2305-5839.2015.12.63
      5. Qiu Z, Chen X, Geng T, Wan Z, Lu Q, Li L, et al. Associations of serum carotenoids with risk of cardiovascular mortality among individuals with type 2 diabetes: results from NHANES. Diabetes Care 2022;45(6):1453-61. doi: 10.2337/dc21-2371.

      6. Jaddoe VW, de Jonge LL, Hofman A, Franco OH, Steegers EA, Gaillard R. First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study. BMJ. 2014;348:g14. doi: 10.1136/bmj.g14.

        • Bjerregaard L.G.
        • Pedersen D.C.
        • Mortensen E.L.
        • Sorensen T.I.A.
        • Baker J.L.
        Breastfeeding duration in infancy and adult risks of type 2 diabetes in a high-income country.
        Matern Child Nutr. 2019; 15: e12869
        • Ricci C.
        • Schutte A.E.
        • Schutte R.
        • Smuts C.M.
        • Pieters M.
        Trends in alcohol consumption in relation to cause-specific and all-cause mortality in the United States: a report from the NHANES linked to the US mortality registry.
        Am J Clin Nutr. 2020; 111: 580-589https://doi.org/10.1093/ajcn/nqaa008
        • VanderWeele T.J.
        • Ding P.
        Sensitivity analysis in observational research: introducing the E-value.
        Ann Intern Med. 2017; 167: 268-274https://doi.org/10.7326/M16-2607
        • Haneuse S.
        • VanderWeele T.J.
        • Arterburn D.
        Using the E-value to assess the potential effect of unmeasured confounding in observational studies.
        JAMA. 2019; 321: 602-603https://doi.org/10.1001/jama.2018.21554
        • Mo Y.
        • Ma X.
        • Li H.
        • Ran X.
        • Yang W.
        • Li Q.
        • et al.
        Relationship between glycated albumin and glycated hemoglobin according to glucose tolerance status: a multicenter study.
        Diabetes Res Clin Pract. 2016; 115: 17-23
        • Imai T.
        • Oikawa Y.
        • Shimada A.
        Improved monitoring of the hyperglycemic state in type 1 diabetes patients by use of the glycoalbumin/HbA1c ratio.
        Rev Diabet Stud. 2007; 4: 44-48https://doi.org/10.1900/RDS.2007.4.44
        • Kim D.
        • Kim K.J.
        • Huh J.H.
        • Lee B.-W.
        • Kang E.S.
        • Cha B.S.
        • et al.
        The ratio of glycated albumin to glycated haemoglobin correlates with insulin secretory function.
        Clin Endocrinol (Oxf). 2012; 77: 679-683
        • Day J.F.
        • Ingebretsen C.G.
        • Ingebretsen Jr., W.R.
        • Baynes J.W.
        • Thorpe S.R.
        Nonenzymatic glucosylation of serum proteins and hemoglobin: response to changes in blood glucose levels in diabetic rats.
        Diabetes. 1980; 29: 524-527https://doi.org/10.2337/diab.29.7.524
        • Anguizola J.
        • Matsuda R.
        • Barnaby O.S.
        • Hoy K.S.
        • Wa C.
        • DeBolt E.
        • et al.
        Review: Glycation of human serum albumin.
        Clin Chim Acta. 2013; 425: 64-76
        • Quincozes-Santos A.
        • Bobermin L.D.
        • de Assis A.M.
        • Goncalves C.A.
        • Souza D.O.
        Fluctuations in glucose levels induce glial toxicity with glutamatergic, oxidative and inflammatory implications.
        Biochim Biophys Acta Mol Basis Dis. 2017; 1863: 1-14https://doi.org/10.1016/j.bbadis.2016.09.013
        • Virtue M.A.
        • Furne J.K.
        • Nuttall F.Q.
        • Levitt M.D.
        Relationship between GHb concentration and erythrocyte survival determined from breath carbon monoxide concentration.
        Diabetes Care. 2004; 27: 931-935https://doi.org/10.2337/diacare.27.4.931
      7. Wang N, Xu Z, Han P, Li T. Glycated albumin and ratio of glycated albumin to glycated hemoglobin are good indicators of diabetic nephropathy in type 2 diabetes mellitus. Diabetes Metab Res Rev. 2017;33(2). doi: 10.1002/dmrr.2843.

        • Umayahara Y.
        • Fujita Y.
        • Watanabe H.
        • Kasai N.
        • Fujiki N.
        • Hatazaki M.
        • et al.
        Association of glycated albumin to HbA1c ratio with diabetic retinopathy but not diabetic nephropathy in patients with type 2 diabetes.
        Clin Biochem. 2017; 50: 270-273
        • Yoon H.-J.
        • Lee Y.-h.
        • Kim K.J.
        • Kim S.R.
        • Kang E.S.
        • Cha B.-S.
        • et al.
        Glycated albumin levels in patients with type 2 diabetes increase relative to HbA1c with time.
        Biomed Res Int. 2015; 2015: 1-8
        • Ohara T.
        • Furuta Y.
        • Hirabayashi N.
        • Hata J.
        • Hirakawa Y.
        • Honda T.
        • et al.
        Elevated serum glycated albumin and glycated albumin: hemoglobin A1c ratio were associated with hippocampal atrophy in a general elderly population of Japanese: the Hisayama Study.
        J Diabetes Investig. 2020; 11: 971-979https://doi.org/10.1111/jdi.13220
        • Zhong Y.
        • Jin J.
        • Xu C.C.
        • Fu G.X.
        GA to HbA1C ratio, but not HbA1C is associated with cognition in Chinese nondiabetic old adults.
        Aging Ment Health. 2015; 19: 853-857https://doi.org/10.1080/13607863.2014.977773
        • Strain W.D.
        • Paldanius P.M.
        Diabetes, cardiovascular disease and the microcirculation.
        Cardiovasc Diabetol. 2018; 17: 57https://doi.org/10.1186/s12933-018-0703-2
        • Monnier L.
        • Mas E.
        • Ginet C.
        • Michel F.
        • Villon L.
        • Cristol J.P.
        • et al.
        Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes.
        JAMA. 2006; 295: 1681-1687https://doi.org/10.1001/jama.295.14.1681
      8. Martinez M, Santamarina J, Pavesi A, Musso C, Umpierrez GE. Glycemic variability and cardiovascular disease in patients with type 2 diabetes. BMJ Open Diabetes Res Care 2021;9(1): e002032. doi: 10.1136/bmjdrc-2020-002032.

        • Yang P.
        • Feng J.
        • Peng Q.
        • Liu X.
        • Fan Z.
        Advanced glycation end products: potential mechanism and therapeutic target in cardiovascular complications under diabetes.
        Oxid Med Cell Longev. 2019; 2019: 9570616https://doi.org/10.1155/2019/9570616
        • Selvin E.
        • Rawlings A.M.
        • Lutsey P.L.
        • Maruthur N.
        • Pankow J.S.
        • Steffes M.
        • et al.
        Fructosamine and glycated albumin and the risk of cardiovascular outcomes and death.
        Circulation. 2015; 132: 269-277
      9. Daya NR, Rooney MR, Tang O, Coresh J, Christenson RH, Selvin E. Glycated albumin in pristine and non-pristine stored samples in the national health and nutrition examination survey (NHANES) 1999-2004. J Appl Lab Med. 2022. doi: 10.1093/jalm/jfab168.

        • He X.
        • Mo Y.
        • Ma X.
        • Ying L.
        • Zhu W.
        • Wang Y.
        • et al.
        Associations of body mass index with glycated albumin and glycated albumin/glycated hemoglobin A1c ratio in Chinese diabetic and non-diabetic populations.
        Clin Chim Acta. 2018; 484: 117-121
      10. Huh JH, Kim KJ, Lee BW, Kim DW, Kang ES, Cha BS, et al. The relationship between BMI and glycated albumin to glycated hemoglobin (GA/A1c) ratio according to glucose tolerance status. PLoS One 2014;9(2):e89478. doi: 10.1371/journal.pone.0089478.

        • Cheng Y.J.
        • Kanaya A.M.
        • Araneta M.R.G.
        • Saydah S.H.
        • Kahn H.S.
        • Gregg E.W.
        • et al.
        Prevalence of diabetes by race and ethnicity in the United States, 2011–2016.
        JAMA. 2019; 322: 2389https://doi.org/10.1001/jama.2019.19365