Clinlab Navigator

Hemoglobin A1c and Aging

Hemoglobin A1c (HbA1c) refers to a minor population of HbA that has been modified by attachment of glucose to the N-terminal amino acid of the beta globin chain. Since erythrocytes are freely permeable to glucose, the attachment occurs continually over the entire lifespan of the erythrocyte and is dependent on glucose concentration and the duration of exposure of the erythrocyte to blood glucose. HbA1c is a weighted average of blood glucose levels during the preceding 120 days, which is the average life span of red blood cells.

HbA1c provides a much better indication of long-term glycemic control than blood and urinary glucose determinations. There is broad consensus that HbA1c levels should be used for routine care of all patients with diabetes mellitus. Baseline HbA1c levels are strongly related to the incidence and/or progression of retinopathy, gross proteinuria, and loss of tactile sensation or temperature sensitivity.

The reference range of 4.0-5.6% was established in 1986 based on 124 nondiabetic individuals between the ages of 13 and 39 years of age. In 1994, the UK Prospective Diabetes Study found the upper limit of the reference range to be 5.4% in 195 healthy persons 25 to 65 years old and 5.6% in 53 healthy persons over 65 years of age.

Recent studies suggest that this reference range may not be valid for older adults. A 2019 study of 1804 healthy men and women participating in the Study of Health in Pomerania (SHIP) trials in Germany found that HbA1c levels increased with age in nondiabetic patients. HbA1c increased by 0.15% per decade in men and 0.19% per decade in women. The investigators derived the following age-dependent HbA1c reference ranges.

Age HbA1c (%) Upper Reference Limit
20-39 6.0
40-59 6.2
60 and older 6.5


In 2009, an International Expert Committee recommended the use of the HbA1c test to diagnose diabetes, with a threshold of 6.5% or greater (Diabetes Care 2009, 32 (7):1327-1334). The American Diabetes Association adopted this criterion in 2010. The diagnostic cut point of 6.5% was recommended based on the risk for developing microvascular complications such as retinopathy. Patients who have an HbA1c of 5.7 to 6.4% were considered at high risk for developing diabetes and cardiovascular disease in the future. These individuals were referred to as having prediabetes.

It is important to note that the recent study determined population based upper reference limits for HbA1c while the original studies derived outcomes based upper limits. Further investigation is needed to reconcile these findings.

A related community-based cohort study of 3412 older adults without diabetes who were enrolled in the Atherosclerosis Risk in Communities Study investigated the rate of progression of prediabetes to diabetes. The mean age of participants was 75.6 years. Patients were diagnosed as having prediabetes if they had a HbA1c of 7.7 to 6.4%, fasting glucose level of 100 to 125 mg/dL, either, or both. Interestingly, only 9% of patients with prediabetes progressed to diabetes during the 6.5-year follow-up period.

Together, these studies suggest that awareness of age-dependent increases in HbA1c and the low risk of prediabetes progression in older patients may prevent overdiagnosis and overtreatment of this patient population.


Masuch A, Friedrich N, Roth J, Nauck M, et al. Preventing misdiagnosis of diabetes in the elderly: age-dependent HbA1c reference intervals derived from two population-based study cohorts. BMC Endocr Disord. 2019.19, 20.

Rooney M, Rawlings A, Pankow J. Risk of progression to diabetes among older adults with prediabetes. JAMA Intern Med. 2021;181(4):511-519. doi:10.1001/jamainternmed.2020.8774.

AddThis Social Bookmark Button