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DOI: 10.1055/s-0042-105440
HbA1c and Age in Non-Diabetic Subjects: An Ignored Association?
Publication History
received 15 February 2016
revised 19 March 2016
accepted 23 March 2016
Publication Date:
24 May 2016 (online)
![](https://www.thieme-connect.de/media/eced/201610/lookinside/thumbnails/02-2016-0082-dia_10-1055-s-0042-105440-1.jpg)
Abstract
Objective: Target HbA1c values given in the most National Therapeutic Guidelines for patients with diabetes and cut-off HbA1c values for diabetes diagnosis are usually not taking the age of the respective patients into account; despite the fact that an increase in HbA1c in subjects without diabetes with age is known for some time. In order to further quantify the association between age and HbA1c in non-diabetic subjects an analysis of one German register was performed.
Methods: In this cross-sectional study we analyzed data from 7 699 visits of 2 921 patients without diabetes (age 46.6 y [range 18–93 y]; 69.1% women; BMI 27.6±6.4 kg/m²) who had at least one HbA1c and blood glucose measurement. Data were drawn from an electronic patient record system (EMIL™) in which data were collected between 01/1992 and 01/2014. The patients were divided in 6 age groups (< 30 years [n=1 057];>30–40 years [n=1 160];>40–50 years [n=1 693];>50–60 years [n=1 523];>60–70 years [n=1 310];>70 years [n=956]) and the HbA1c values of these groups were compared. Patients with: gestational diabetes, use of systemic glucocorticoids, malignant neoplasm, age<18 y at time of first visit and IGT were excluded. HbA1c measurements were DCCT adjusted.
Results: Patients with age>70 years have a 0.47% [5.14 mmol/mol] higher HbA1c compared to those<30 years. The mean HbA1c of the age groups was:<30 4.98% [30.96 mmol/mol],>30–40 5.07% [31.99 mmol/mol],>40–50 5.17% [33.10 mmol/mol],>50–60 5.33% [34.79 mmol/mol],>60–70 5.42% [35.79 mmol/mol] and>70 years 5.45% [36.10 mmol/mol]. In a multiple linear model the regression coefficient for each year of age increase was β=0.0074 (p<0.001); thus age results in an increase of 0.074% in HbA1c per decade.
Conclusion: HbA1c increases significantly with ageing in people without diabetes. The use of different cut-off values for every age range for diagnosis of diabetes should be discussed.
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References
- 1 Pani LN, Korenda L, Meigs JB et al. Effect of aging on A1C levels in individuals without diabetes: evidence from the Framing-ham Offspring Study and the National Health and Nutrition Examination Survey 2001–2004. Diabetes Care 2008; 31: 1991-1996
- 2 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: 2193-2193
- 3 Nakashima K, Nishizaki O, Andoh Y. Acceleration of hemoglobin glycation with aging. ClinChim Acta 1993; 214: 111-118
- 4 Hashimoto Y, Futamura A, Ikushima M. Effect of aging on HbA1c in a working male Japanese population. Diabetes Care 1995; 18: 1337-1340
- 5 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
- 6 Nuttall QF. Effect of age on percentage of hemoglobin A1c and the percentage of total glycohemoglobin in non-diabetic persons. J Lab Clin Med 1999; 134: 451-453
- 7 Kabadi UM. Glycosylation of proteins. Lack of influence of aging. Diabetes Care 1988; 11: 429-432
- 8 Wiener K, Roberts NB. Age does not influence levels of HbA1c in normal subject. QJM 1999; 92: 169-173
- 9 Vallee Polneau S, Lasserre V, Fonfrede M et al. A different approach to analyzing age-related HbA1c values in nondiabetic subjects. ClinChem Lab Med 2004; 42: 423-428
- 10 Mulkerrin EC, Arnold JD, Dewar R et al. Glycosylated hemoglobin in the diagnosis of diabetes mellitus in elderly people. Age Ageing 1992; 21: 175- 177
- 11 Müller N, Heller T, Freitag M et al. Healthcare utilization of people with Type 2 diabetes in Germany: an analysis based on health insurance data. Diabet Med 2015; 32: 951-957
- 12 Selvin E, Coresh J, Brancati F. The burden and treatment of diabetes in elderly individuals in the U.S. Diabetes Care 2006; 29: 2415-2419
- 13 The Diabetes Control and Complications Trial (DCCT): Design and methodological considerations for the feasibility phase: the DCCT Research Group. Diabetes 1986; 35: 530-545
- 14 American Diabetes Association . Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2010; 33: 62-69
- 15 American Diabetes Association . Standards of medical care in diabetes. Diabetes Care 2015; 38: 1-93
- 16 German Medical Association, National Association of Statutory Health Insurance Physicians, Association of the Scientific Medical Societies in Germany: National guidelines Therapy of Type 2 diabetes – long version. Version 2. 2013. Available at http://www.versorgungsleitlinien.de/themen/diabetes2/dm2_therapie/pdf/NVL-DM2-Ther-lang-2.pdf Accessed July 13, 2015
- 17 National Institute for Health and Clinical Excellence . Diabetes mellitus Type 2: Diagnosis, Prevention and Management (Clinical Guideline 87). Available at: http://pathways.nice.org.uk/pathways/diabetes#path=view%3A/pathways/diabetes/blood-glucose-lowering-therapy-for-type-2-diabetes.xml&content=view-index Accessed July 4, 2015
- 18 World Health Organization . Guidelines Review Committee. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes mellitus. Abbreviated Report of a WHO Consultation. Geneva: World Health Organization; 2011
- 19 Canadian Diabetes Association . Clinical practice guidelines for Diabetes mellitus Type 2. Available at: http://guidelines.diabetes.ca/bloodglucoselowering/a1ctarget Accessed July 4, 2015
- 20 Halwachs-Baumann G, Katzensteiner S, Schnedl W et al. Comparative evaluation of three assay systems for automated determination of hemoglobin A1c. Clin Chem 1997; 43: 511-517
- 21 Chapelle JP, Teixeira J, Maisin D et al. Multicentre evaluation of the Tosoh HbA1c G8 analyser. Clin Chem Lab Med 2010; 48: 365-371
- 22 Gould BJ, Davie SJ, Yudkin JS. Investigation of the mechanism underlying the variability of Glycated haemoglobin in non-diabetic subjects not related to glycaemia. ClinChim Acta 1997; 260: 49-64
- 23 Flückiger R, Harmon W, Meier W et al. Hemoglobin carbamylation in uremia. N Engl J Med 1981; 304: 823-827
- 24 Schmitz O. Glucose metabolism in non-diabetic and insulin-dependent diabetic subjects with end-stage renal failure. Dan Med Bull 1991; 38: 36-52
- 25 Müller UA, Müller N, Heller T et al. Vergleichbarkeit von HbA1c-Bestimmungen mit drei verschiedenen Methoden an vier regionalen Standorten 2013. Diabetologie und Stoffwechsel 2014. Available at https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1375021 Accessed: June 23, 2015
- 26 Modan M, Meytes D, Roseman P et al. Significance of high HbA1c levels in normal glucose tolerance. Diabetes Care 1988; 11: 422-428
- 27 Yudkin JS, Forrest RD, Jackson CA et al. Unexplained variability of glycated hemoglobin in non-diabetic subjects not related to glycaemia. Diabetologia 1990; 33: 208-215