Effects of HbA1c variability on serious infection risks and the influence of age, sex, and ethnicity: a primary care cohort of patients with type 2 diabetes

Conference:

SAPC ASM 2024 - Bristol

Talk Code:

5C.2

Presenter:

Liza Bowen

Co-authors:

Iain M Carey, Julia A Critchley, Umar A R Chaudhry, Derek G Cook, Stephen DeWilde, Elizabeth S Limb, Liza Bowen, Stephen Woolford, Peter H Whincup, Tess Harris

Author institutions:

St George's, University of London

Problem

Long-term HbA1c variability is associated with micro- and macro-vascular complications in type 2 diabetes, but it is not well established if it also increases the risk of infections. We explored prospective associations between HbA1c variability and serious infection; how these relate to HbA1c average level, and whether these are modified by age, sex, and ethnicity.

Approach

411,963 patients with type 2 diabetes in England, aged 18-90, alive on 01/01/2015 in the Clinical Practice Research Datalink were included. HbA1c measurements made during 2011-14 were used to estimate an average level and a HVS variability score (HVS). The HVS counts how frequently HbA1c rises or decreases by a fixed threshold or more, across a series of successive measurements made over time and is summarised as a percentage (0-100). Poisson regression estimated incidence rate ratios (IRRs) for infections requiring hospitalisation during 2015-19 by HVS categories, adjusting for confounders, stratified by age, sex, ethnicity and average HbA1c level. To compare the potential overall impact of variability versus average level, attributable risk fractions (AF) were calculated. These estimate the proportion of all infections attributable to higher variability or average level compared to a hypothetical reference category for both variability (HVS 0-20) and average level (42-48mmol/mol).

Findings

While increasing HbA1c level and variability were both independently associated with infections, a greater infection risk (IRR>1.2) was seen with modest variability (HVS≥20, 73% of patients). However, infection risk was elevated only at higher average levels (≥64mmol/mol, 27% of patients). Estimated AFs were markedly greater for variability than average level (17.1% vs. 4.1%). The positive association between variability and infection was more apparent among patients with the lowest average HbA1c levels (<48 mmol/mol) and observed at all levels except the very highest (≥86 mmol/mol). Associations with variability were greater among older patients (>60y) and those with lower HbA1c levels, and not observed among people from Black ethnicities. Associations were similar whatever the direction of the last recorded HbA1c change.

Consequences

At a population level, HbA1c variability between primary care visits among patients with type 2 diabetes appears to account for more serious infections than average HbaA1c level. Since individual risks with variability were observed at lower average levels, greater clinician and patient awareness of HbA1c variability may be beneficial. However, only well-designed trials can establish whether there are long-term benefits of directly treating variability in HbA1c on infections, quality of life and other diabetes complications.

Submitted by:

Liza Bowen

Funding acknowledgement:

This study is funded by the National Institute for Health and Care Research (NIHR) - Research for Patient Benefit Programme (NIHR202213) and supported by the NIHR Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust.