Glycaemic markers and all-cause mortality in older adults with and without diabetes: the Atherosclerosis Risk in Communities (ARIC) study

Abstract

Aims/hypothesis: There is controversy regarding the performance of HbA_1c in old age. We evaluated the prognostic value of HbA_1c and other glycaemic markers (fructosamine, glycated albumin, fasting glucose) with mortality risk in older adults (66-90 years).

Methods: This was a prospective analysis of 5636 participants (31% with diagnosed diabetes, mean age 76, 58% female, 21% black) in the Atherosclerosis Risk in Communities (ARIC) study, baseline 2011-2013. We used Cox regression to examine associations of glycaemic markers (modelled in categories) with mortality risk, stratified by diagnosed diabetes status.

Results: During a median of 6 years of follow-up, 983 deaths occurred. Among older adults with diabetes, 30% had low HbA_1c (<42 mmol/mol [<6.0%]) and 10% had high HbA_1c (≥64 mmol/mol [≥8.0%]); low (HR 1.32 [95% CI 1.04, 1.68]) and high (HR 1.86 [95% CI 1.32, 2.62]) HbA_1c were associated with mortality risk vs HbA_1c 42-52 mmol/mol (6.0-6.9%) after demographic adjustment. Low fructosamine and glycated albumin were not associated with mortality risk. Both low and high fasting glucose were associated with mortality risk. After further adjustment for lifestyle and clinical risk factors, high HbA_1c (HR 1.81 [95% CI 1.28, 2.56]), fructosamine (HR 1.96 [95% CI 1.43-2.69]), glycated albumin (HR 1.81 [95% CI 1.33-2.47]) and fasting glucose (HR 1.81 [95% CI 1.24, 2.66]) were associated with mortality risk. Low HbA_1c and fasting glucose were no longer significantly associated with mortality risk. Among participants without diabetes, associations of glycaemic markers with mortality risk were less robust.

Conclusions/interpretation: Elevated HbA_1c, fructosamine, glycated albumin and fasting glucose were associated with risk of mortality in older adults with diabetes. Low HbA_1c and fasting glucose may be markers of poor prognosis but are possibly confounded by health status. Our findings support the clinical use of HbA_1c in older adults with diabetes. Graphical abstract.

Keywords: Ageing; Biomarker; Blood; Diabetes; Glucose; HbA1c; Mortality; Prospective.

Fig. 1

Associations of glycaemic markers with all-cause mortality, stratified by diabetes diagnosis status (a–d, no diagnosed diabetes; e–h, diagnosed diabetes), for the ARIC study 2011–2018, showing HR (95% CI) and proportion of the population (%). Restricted cubic splines adjusted for age, sex and race. Knots at 5th, 35th, 65th, and 95th percentiles, and centred at the median; >99th and <1st percentile removed to minimize influence of extreme values and for ease of display