Long-term Visit-to-Visit Variability in Hemoglobin A1c and Kidney-Related Outcomes in Persons With Diabetes

Am J Kidney Dis. 2023 May 12;S0272-6386(23)00628-5. doi: 10.1053/j.ajkd.2023.03.007. Online ahead of print.


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.