ReviewDiabetology & metabolic syndrome2026
Glycemic instability in renal decline: a review of HbA1c variability and outcomes in chronic kidney disease.
Review in Diabetology & metabolic syndrome, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDiabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), and glycemic assessment is complicated by altered glucose/insulin handling and biased glycated hemoglobin (HbA1c) values in advanced kidney disease. Beyond mean HbA1c, long-term visit-to-visit HbA1c variability has emerged as an additional dimension of risk. This review aims to summarize the definition, measurement, and clinical significance of long-term HbA1c variability in diabetes with CKD, and to discuss implications for risk stratification and management, including complementary biomarkers and continuous glucose monitoring (CGM).
methodsWe narratively reviewed observational cohorts, meta-analyses, and dialysis/advanced CKD studies evaluating metrics of long-term glycemic variability (e.g., HbA1c-standard deviation, HbA1c-coefficient of variation, HbA1c variability score) and their associations with renal outcomes, cardiovascular events, and mortality, alongside evidence on alternative biomarkers and CGM-derived indices.
resultsAcross diverse populations, higher HbA1c variability is consistently associated with faster CKD progression, greater risk of ESKD, increased cardiovascular events, and higher all-cause mortality, often independent of mean HbA1c. In advanced CKD and dialysis, HbA1c limitations and treatment-related glucose swings heighten the value of CGM and, in selected settings, glycated albumin/fructosamine.
conclusionLong-term HbA1c variability is a robust prognostic marker in diabetic CKD and should complement mean HbA1c in clinical assessment; prospective trials are needed to test whether variability-targeted strategies improve hard outcomes.
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