Rational & objective: To characterize associations between long-term visit-to-visit variability of HbA1c 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 HbA1c variability score (HVS, the percentage of total HbA1c 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.
Outcomes: CKD progression (composite of >50% eGFR decline and kidney failure), AKI (by clinical diagnosis or transient creatinine elevations according to KDIGO criteria), and worsening of albuminuria.
Analytical approach: Multivariable Cox proportional hazards regression.
Results: Compared with persons showing low HbA1c variability (HVS 0-20%), any increase in variability was associated with a higher risk of adverse kidney outcomes beyond mean HbA1c. For example, for patients with a baseline HbA1c 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 [1.21-1.36] for worsening of albuminuria. Results were consistent across subgroups (diabetes subtypes, baseline eGFR or albuminuria categories), in time-varying analyses and in sensitivity analyses including time-weighted average HbA1c or alternative metrics of variability.
Limitations: Observational study, limitations of claims data, lack of information on diet, BMI, 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.
Keywords: AKI; CKD progression; Diabetes; HbA1c variability; worsening of albuminuria.
Copyright © 2023. Published by Elsevier Inc.