Long-term visit-to-visit variability in hemoglobin A1c and kidney-related outcomes in persons with diabetes

Abstract

Rationale & Objective: To characterize associations between long-term visit-to-visit variability of hemoglobin A(1c) (HbA(1c)) and risk of adverse kidney outcomes in patients with diabetes.Study Design: Observational study.Setting & Participants: 93,598 adults with diabetes undergoing routine care in Stockholm, Sweden.Exposures and Predictors: Categories of baseline and time-varying HbA(1c) variability score (HVS, the percentage of total HbA(1c) measures that vary by >0.5% [5.5 mmol/mol] during a 3-year window): 0-20%, 21%-40%, 41%-60%, 61%-80%, and 81%-100%, with 0-20% as the reference group.Outcome: Chronic kidney disease (CKD) progression (composite of >50% estimated glomerular filtration rate [eGFR] decline and kidney failure), acute kidney disease (AKI by clinical diagnosis or transient creatinine elevations ac-cording to KDIGO criteria), and worsening of albuminuria.Analytical Approach: Multivariable Cox proportional hazards regression.Results: Compared with persons showing low HbA(1c) variability (HVS 0-20%), any increase in variability was associated with a higher risk of adverse kidney outcomes beyond mean HbA(1c). For example, for patients with a baseline HbA(1c) variability of 81%-100%, the adjusted HR was 1.6 (95% CI, 1.47-1.74) for CKD progression, 1.23 [1.16-1.3] for AKI, and 1.28 [1.21-1.3 6] for worsening of albuminuria. The results were consistent across subgroups (diabetes subtypes, baseline eGFR, or albuminuria categories), in time-varying analyses and in sensitivity analyses including time-weighted average HbA(1c) or alternative metrics of variability.Limitations: Observational study, limitations of claims data, lack of information on diet, body mass index, medication changes, and diabetes duration.Conclusions: Higher long-term visit-to-visit HbA1c variability is consistently associated with the risks of CKD progression, AKI, and worsening of albuminuria.