Reconsidering the HbA1c Cutoff for Diabetes Diagnosis Based on a Large Chinese Cohort

 

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Abstract

Introduction The HbA1c has been considered as the ‘gold standard’ in diabetes diagnosis and management, however, age, gender and body mass index (BMI) might have certain effects on HbA1c. We are aiming to further investigate the correlation between age and HbA1c, and whether it was affected by gender and BMI.

Methods A cross-sectional survey including 135,893 nondiabetic individuals who took the physical examination between 2013 and 2017 was conducted. The subjects were grouped by gender, age and BMI, and the interactive and independent effects of the 3 factors on the HbA1c were detected. The median and 95% confidence interval (CI) of HbA1c levels were calculated.

Results The HbA1c levels gradually increased along with age, both in female and male, and there is a positive association between BMI and the HbA1c. The difference on HbA1c in gender was associated with both age and BMI, the age-related increase in HbAlc was accentuated in the subgroup with higher BMI, and there was a marked accentuation of the positive association between BMI and HbA1c as age increased. In almost all the young and middle-aged (aged 20–59) subgroups, the 97.5^th percentiles of HbA1c levels were lower than 6.5%, suggesting that the single HbA1c cutoff value is probably not applicable to the young and middle-aged population.

Conclusions We recommend that the effects of age, gender and BMI should be taken into consideration when using HbA1c for the diagnosis and management of diabetes, especially in the young and middle-aged population.

^* Jiying Qi and Yang Su contributed equally to this work.

Publication History

Received: 07 February 2018
Received: 27 June 2018

Accepted: 14 January 2019

Article published online:
30 April 2019

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• References

• 1 Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87: 4-14
  CrossrefPubMedGoogle Scholar
• 2 Wang L, Gao P, Zhang M. et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA 2017; 317: 2515-2523
  CrossrefPubMedGoogle Scholar
• 3 Allen DW, Schroeder WA, Balog J. Observations on the chromatographic heterogeneity of normal adult and fetal human hemoglobin: a study of the effects of crystallization and chromatography on the heterogeneity and isoleucine content. Journal of the American Chemical Society 1958; 80: 2617-2622
  CrossrefPubMedGoogle Scholar
• 4 Rahbar S. An abnormal hemoglobin in red cells of diabetics. Clin Chim Acta 1968; 22: 296-298
  CrossrefPubMedGoogle Scholar
• 5 Rahbar S, Blumenfeld O, Ranney HM. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun 1969; 36: 838-843
  CrossrefPubMedGoogle Scholar
• 6 Consensus statement on the worldwide standardisation of the HbA1c measurement . Diabetologia. 2007; 50: 2042-2043
  PubMedGoogle Scholar
• 7 International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes . Diabetes Care. 2009; 32: 1327-1334
  PubMedGoogle Scholar
• 8 American Diabetes A . Standards of medical care in diabetes–2010. Diabetes Care 2010; 33 (Suppl 1): S11-S61
  CrossrefPubMedGoogle Scholar
• 9 American Diabetes A . Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 (Suppl 1): S62-S69
  CrossrefPubMedGoogle Scholar
• 10 Colagiuri S, Lee CM, Wong TY. et al. Glycemic thresholds for diabetes-specific retinopathy: Implications for diagnostic criteria for diabetes. Diabetes Care 2011; 34: 145-150
  CrossrefPubMedGoogle Scholar
• 11 Davidson MB, Schriger DL, Peters AL. et al. Relationship between fasting plasma glucose and glycosylated hemoglobin: Potential for false-positive diagnoses of type 2 diabetes using new diagnostic criteria. Jama 1999; 281: 1203-1210
  CrossrefPubMedGoogle Scholar
• 12 Engelgau MM, Thompson TJ, Herman WH. et al. Comparison of fasting and 2-hour glucose and HbA1c levels for diagnosing diabetes. Diagnostic criteria and performance revisited. Diabetes Care 1997; 20: 785-791
  CrossrefPubMedGoogle Scholar
• 13 Arnetz BB, Kallner A, Theorell T. The influence of aging on hemoglobin A1c (HbA1c). Journal of Gerontology 1982; 37: 648-650
  CrossrefPubMedGoogle Scholar
• 14 Hashimoto Y, Futamura A, Ikushima M. Effect of aging on HbA1c in a working male Japanese population. Diabetes Care 1995; 18: 1337-1340
  CrossrefPubMedGoogle Scholar
• 15 Pani LN, Korenda L, Meigs JB. et al. Effect of aging on A1C levels in individuals without diabetes: Evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001-2004. Diabetes Care 2008; 31: 1991-1996
  CrossrefPubMedGoogle Scholar
• 16 Simon D, Senan C, Garnier P. et al. Epidemiological features of glycated haemoglobin A1c-distribution in a healthy population. The Telecom Study. Diabetologia 1989; 32: 864-869
  CrossrefPubMedGoogle Scholar
• 17 Carrera T, Bonamusa L, Almirall L. et al. Should age and sex be taken into account in the determination of HbA1c reference range?. Diabetes Care 1998; 21: 2193-2194
  CrossrefPubMedGoogle Scholar
• 18 Yang YC, Lu FH, Wu JS. et al. Age and sex effects on HbA1c. A study in a healthy Chinese population. Diabetes Care 1997; 20: 988-991
  CrossrefPubMedGoogle Scholar
• 19 Selvin E, Zhu H, Brancati FL. Elevated A1C in adults without a history of diabetes in the U.S. Diabetes Care 2009; 32: 828-833
  CrossrefPubMedGoogle Scholar
• 20 Ravikumar P, Bhansali A, Walia R. et al. Alterations in HbA(1c) with advancing age in subjects with normal glucose tolerance: Chandigarh Urban Diabetes Study (CUDS). Diabet Med 2011; 28: 590-594
  CrossrefPubMedGoogle Scholar
• 21 Saltevo JT, Kautiainen H, Niskanen L. et al. Ageing and associations of fasting plasma glucose and 2 h plasma glucose with HbA(1C) in apparently healthy population. “FIN-D2D” study. Diabetes Res Clin Pract 2011; 93: 344-349
  CrossrefPubMedGoogle Scholar
• 22 Inoue M, Inoue K, Akimoto K. Effects of age and sex in the diagnosis of type 2 diabetes using glycated haemoglobin in Japan: The Yuport Medical Checkup Centre study. PLoS One 2012; 7: e40375
  CrossrefPubMedGoogle Scholar
• 23 Xu Y, Wang L, He J. et al. Prevalence and control of diabetes in Chinese adults. JAMA 2013; 310: 948-959
  CrossrefPubMedGoogle Scholar
• 24 Dubowitz N, Xue W, Long Q. et al. Aging is associated with increased HbA1c levels, independently of glucose levels and insulin resistance, and also with decreased HbA1c diagnostic specificity. Diabet Med 2014; 31: 927-935
  CrossrefPubMedGoogle Scholar
• 25 Pieri M, Pignalosa S, Zenobi R. et al. Reference intervals for HbA1c partitioned for gender and age: A multicenter study. Acta Diabetol 2016; 53: 1053-1056
  CrossrefPubMedGoogle Scholar
• 26 Kabadi UM. Glycosylation of Proteins: Lack of Influence of Aging. Diabetes Care 1988; 11: 429-432
  CrossrefPubMedGoogle Scholar
• 27 Wiener K, Roberts NB. Age does not influence levels of HbA1c in normal subject. QJM : Monthly journal of the Association of Physicians 1999; 92: 169-173
  CrossrefPubMedGoogle Scholar
• 28 Vallee Polneau S, Lasserre V, Fonfrede M. et al. A different approach to analyzing age-related HbA1c values in non-diabetic subjects. Clin Chem Lab Med 2004; 42: 423-428
  PubMedGoogle Scholar
• 29 Hu D, Henderson JA, Welty TK. et al. Glycemic control in diabetic American Indians. Longitudinal data from the Strong Heart Study. Diabetes Care 1999; 22: 1802-1807
  CrossrefPubMedGoogle Scholar
• 30 Gilliland SS, Carter JS, Skipper B. et al. HbA(1c) levels among American Indian/Alaska Native adults. Diabetes Care 2002; 25: 2178-2183
  CrossrefPubMedGoogle Scholar
• 31 Hessler DM, Fisher L, Mullan JT. et al. Patient age: A neglected factor when considering disease management in adults with type 2 diabetes. Patient Educ Couns 2011; 85: 154-159
  CrossrefPubMedGoogle Scholar
• 32 Guo F, Moellering DR, Garvey WT. Use of HbA1c for diagnoses of diabetes and prediabetes: Comparison with diagnoses based on fasting and 2-hr glucose values and effects of gender, race, and age. Metab Syndr Relat Disord 2014; 12: 258-268
  CrossrefPubMedGoogle Scholar
• 33 Kramer CK, Araneta MR, Barrett-Connor E. A1C and diabetes diagnosis: The Rancho Bernardo Study. Diabetes Care 2010; 33: 101-103
  CrossrefPubMedGoogle Scholar
• 34 Nakagami T, Tominaga M, Nishimura R. et al. Is the measurement of glycated hemoglobin A1c alone an efficient screening test for undiagnosed diabetes? Japan National Diabetes Survey. Diabetes Res Clin Pract. 2007; 76: 251-256
  PubMedGoogle Scholar
• 35 Pinelli NR, Jantz AS, Martin ET. et al. Sensitivity and specificity of glycated hemoglobin as a diagnostic test for diabetes and prediabetes in Arabs. J Clin Endocrinol Metab 2011; 96: E1680-E1683
  CrossrefPubMedGoogle Scholar
• 36 Yan ST, Xiao HY, Tian H. et al. The cutoffs and performance of glycated hemoglobin for diagnosing diabetes and prediabetes in a young and middle-aged population and in an elderly population. Diabetes Res Clin Pract 2015; 109: 238-245
  CrossrefPubMedGoogle Scholar
• 37 Hu Y, Bhupathiraju SN, de Koning L. et al. Duration of obesity and overweight and risk of type 2 diabetes among US women. Obesity (Silver Spring) 2014; 22: 2267-2273
  CrossrefPubMedGoogle Scholar
• 38 Li LM, Rao KQ, Kong LZ. et al. A description on the Chinese national nutrition and health survey in 2002. Chinese Journal of Epidemiology 2005; 26: 478-484
  PubMedGoogle Scholar
• 39 R core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna; Austria: 2017. https://www.R-project.org/
  Google Scholar
• 40 Yates AP, Laing I. Age-related increase in haemoglobin A1c and fasting plasma glucose is accompanied by a decrease in beta cell function without change in insulin sensitivity: Evidence from a cross-sectional study of hospital personnel. Diabet Med 2002; 19: 254-258
  CrossrefPubMedGoogle Scholar
• 41 Wu L, Lin H, Gao J. et al. Effect of age on the diagnostic efficiency of HbA1c for diabetes in a Chinese middle-aged and elderly population: The Shanghai Changfeng Study. PLoS One 2017; 12: e0184607
  CrossrefPubMedGoogle Scholar
• 42 Walton C, Godsland IF, Proudler AJ. et al. The effects of the menopause on insulin sensitivity, secretion and elimination in non-obese, healthy women. Eur J Clin Invest 1993; 23: 466-473
  CrossrefPubMedGoogle Scholar
• 43 Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001; 414: 782-787
  CrossrefPubMedGoogle Scholar
• 44 Qiao Q, Nyamdorj R. Is the association of type II diabetes with waist circumference or waist-to-hip ratio stronger than that with body mass index?. Eur J Clin Nutr 2010; 64: 30-34
  CrossrefPubMedGoogle Scholar
• 45 Chen G, Liu C, Yao J. et al. Overweight, obesity, and their associations with insulin resistance and beta-cell function among Chinese: A cross-sectional study in China. Metabolism: Clinical and experimental 2010; 59: 1823-1832
  CrossrefPubMedGoogle Scholar
• 46 Yang L, Shen X, Yan S. et al. The effectiveness of age on HbA1c as a criterion for the diagnosis of diabetes in Chinese different age subjects. Clin Endocrinol (Oxf) 2015; 82: 205-212
  CrossrefPubMedGoogle Scholar
• 47 Li J, Ma H, Na L. et al. Increased hemoglobin A1c threshold for prediabetes remarkably improving the agreement between A1c and oral glucose tolerance test criteria in obese population. J Clin Endocrinol Metab 2015; 100: 1997-2005
  CrossrefPubMedGoogle Scholar
• 48 Geffre A, Friedrichs K, Harr K. et al. Reference values: A review. Veterinary clinical pathology 2009; 38: 288-298
  CrossrefPubMedGoogle Scholar
• 49 Kerner W, Bruckel J. Definition, classification and diagnosis of diabetes mellitus. Exp Clin Endocrinol Diabetes 2014; 122: 384-386
  Article in Thieme ConnectPubMedGoogle Scholar