Effects of long-term HbA1c variability on serious infection risks in patients with type 2 diabetes and the influence of age, sex and ethnicity: A cohort study of primary care data

Aims: Long-term HbA1c (glycated haemoglobin) variability is associated with micro- and macrovascular complications in Type 2 diabetes (T2D). We explored prospective associations between HbA1c variability and serious infections, and how these vary by HbA1c level, age, sex and ethnicity. Methods: 411,963 T2D patients in England, aged 18-90, alive on 01/01/2015 in the Clinical Practice Research Datalink with >= 4 HbA1c measurements during 2011-14. Poisson regression estimated incidence rate ratios (IRRs) for infections requiring hospitalisation during 2015-19 by HbA1c variability score (HVS) and average level, adjusting for confounders, and stratified by age, sex, ethnicity and average level. Attributable risk fractions (AF) were calculated using reference categories for variability (HVS < 20) and average level (42-48 mmol/mol). Results: An increased infection risk (IRR > 1.2) was seen with even modest variability (HVS >= 20, 73 % of T2D patients), but only at higher average levels (>= 64 mmol/mol, 27 % patients). Estimated AFs were markedly greater for variability than average level (17.1 % vs. 4.1 %). Associations with variability were greater among older patients, and those with lower HbA1c levels, but not observed among Black ethnicities. Conclusions: HbA1c variability between T2D patients' primary care visits appears to be associated with more serious infections than average level overall. Well-designed trials could test whether these associations are causal.