Abstract
Abstract Background and Aims Glycated hemoglobin (HbA1c) is central to the routine monitoring of glycemic control in persons with diabetes, and poor glycemic control is an established contributor to the occurrence and progression of CKD, but whether long-term visit-to-visit variability in glycemic control predicts kidney outcomes is not well studied. Method We included all adults with type 1 or type 2 diabetes in Stockholm, Sweden, during 2006–2019, who had at least one annual outpatient HbA1c test in three consecutive years. We evaluated associations between 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), with the risk of CKD progression (composite of >30% eGFR decline and kidney failure), acute kidney injury (AKI, by clinical diagnosis or increase in creatinine ≥0.3 mg/dL over 48 h or 1.5 times creatinine over 7 days), and worsening of albuminuria. Results We included 93,598 adults with diabetes undergoing 891,536 routine HbA1c tests (median 8 tests per person) during a median follow-up of 5.2 years. Compared with persons showing low HbA1c variability (HVS 0–20%), any increase in variability was associated with a higher risk of adverse kidney outcomes. For example, for patients with a baseline HbA1c variability of 81–100%, the adjusted HR was 1.47 (95% CI, 1.38-1.56) for CKD progression, 1.27 [1.19-1.36] for AKI, and 1.28 [1.21-1.36] for worsening of albuminuria. Results were robust across subgroups (diabetes subtypes, baseline eGFR or albuminuria categories) and in sensitivity analyses including time-weighted average HbA1c or alternative metrics of variability. Conclusion A higher long-term visit-to-visit HbA1c variability is robustly associated with the risks of CKD progression, AKI and worsening of albuminuria.
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