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Observational Study
. 2023 Sep;82(3):267-278.
doi: 10.1053/j.ajkd.2023.03.007. Epub 2023 May 13.

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

Yang Xu  1 , Shujie Dong  2 , Edouard L Fu  3 , Arvid Sjölander  4 , Morgan E Grams  5 , Elizabeth Selvin  6 , Juan Jesus Carrero  7
Affiliations
Observational Study

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

Yang Xu et al. Am J Kidney Dis. 2023 Sep.

Abstract

Rationale & objective: To characterize associations between long-term visit-to-visit variability of hemoglobin A1c (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% [5.5mmol/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 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. 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 HbA1c 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.

Plain-language summary: The evidence for current guideline recommendations derives from clinical trials that focus on a single HbA1c as the definitive measure of efficacy of an intervention. However, long-term visit-to-visit fluctuations of HbA1c may provide additional value in the prediction of future kidney complications. We evaluated the long-term fluctuations in glycemic control in almost 100,000 persons with diabetes undergoing routine care in Stockholm, Sweden. We observed that higher long-term HbA1c fluctuation is consistently associated with the risks of chronic kidney disease progression, worsening of albuminuria and acute kidney injury. This finding supports a role for long-term glycemic variability in the development of kidney complications and illustrates the potential usefulness of this metric for risk stratification at the bedside beyond a single HbA1c test.

Keywords: AKI; CKD progression; HbA(1c) variability; diabetes; worsening of albuminuria.

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Conflict of interest statement

Financial Disclosure: The authors declare that they have no relevant financial interests.

Figures

Figure 1.
Figure 1.
Associations between 3-year baseline HbA1c variability score with kidney-related outcomes. A: CKD progression; B: AKI; C: Worsening of albuminuria. Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease
See this image and copyright information in PMC

Comment in

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