Aging is associated with increased HbA1c levels, independently of glucose levels and insulin resistance, and also with decreased HbA1c diagnostic specificity

Research Article
Aging is associated with increased HbA1c levels, independently of glucose levels and insulin resistance, and also with decreased HbA1c diagnostic specificity

N. Dubowitz, W. Xue, Q. Long, J. G. Ownby, D. E. Olson, D. Barb, M. K. Rhee, A. V. Mohan, P. I. Watson-Williams, S. L. Jackson, A. M. Tomolo, T. M. Johnson II and L. S. Phillips

Diabetic Medicine, 2014, 31(8), 927-935. DOI: 10.1111/dme.12459



To determine whether using HbA1c for screening and management could be confounded by age differences, whether age effects can be explained by unrecognized diabetes and prediabetes, insulin resistance or postprandial hyperglycaemia, and whether the effects of aging have an impact on diagnostic accuracy.


We conducted a cross-sectional analysis in adults without known diabetes in the Screening for Impaired Glucose Tolerance (SIGT) study 2005-2008 (n=1573) and the National Health and Nutrition Examination Survey (NHANES) 2005-2006 (n=1184).


Both glucose intolerance and HbA1c levels increased with age. In univariate analyses including all subjects, HbA1c levels increased by 0.93 mmol/mol (0.085%) per 10 years of age in the SIGT study and by 1.03 mmol/mol (0.094%) per 10 years in the NHANES; in both datasets, the HbA1c increase was 0.87 mmol/mol (0.08%) per 10 years in subjects without diabetes, and 0.76 mmol/mol (0.07%) per 10 years in subjects with normal glucose tolerance, all P<0.001. In multivariate analyses of subjects with normal glucose tolerance, the relationship between age and HbA1c remained significant (P<0.001) after adjustment for covariates including race, BMI, waist circumference, sagittal abdominal diameter, triglyceride/HDL ratio, and fasting and 2-h plasma glucose and other glucose levels, as assessed by an oral glucose tolerance test. In both datasets, the HbA1c of an 80-year-old individual with normal glucose tolerance would be 3.82 mmol/mol (0.35%) greater than that of a 30-year-old with normal glucose tolerance, a difference that is clinically significant. Moreover, the specificity of HbA1c-based diagnostic criteria for prediabetes decreased substantially with increasing age (P<0.0001).


In two large datasets, using different methods to measure HbA1c, the association of age with higher HbA1c levels: was consistent and similar; was both statistically and clinically significant; was unexplained by features of aging; and reduced diagnostic specificity. Age should be taken into consideration when using HbA1c for the diagnosis and management of diabetes and prediabetes.

ASCI-ID: 109-1554

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Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes: a 2-year randomized, treat-to-target trial

Diabetic Medicine, 2013, 30(11), 1298-1304. DOI: 10.1111/dme.12303

The optimal morning:evening ratio in total dose of twice-daily biphasic insulin analogue in poorly controlled Type 2 diabetes: a 24-week multi-centre prospective, randomized controlled, open-labelled clinical study

Diabetic Medicine, 2014, 31(1), 68-75. DOI: 10.1111/dme.12322

Quantification of insulin

Diabetic Medicine, 2014, 31(3), 375-376. DOI: 10.1111/dme.12337

The UK service level audit of insulin pump therapy in adults

Diabetic Medicine, 2014, 31(4), 412-418. DOI: 10.1111/dme.12325

Similar weight-adjusted insulin secretion and insulin sensitivity in short-duration late autoimmune diabetes of adulthood (LADA) and Type 2 diabetes: Action LADA 8

Diabetic Medicine, 2014, 31(8), 941-945. DOI: 10.1111/dme.12434

Serum levels of fractalkine are associated with markers of insulin resistance in gestational diabetes

Diabetic Medicine, 2014, 31(8), 1014-1017. DOI: 10.1111/dme.12451