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. 2025 Aug 1;48(8):1400-1409.
doi: 10.2337/dc25-0339.

The Association Between Hemoglobin A1c and Complications Among Individuals With Diabetes and Severe Chronic Kidney Disease

Dea H Kofod  1 , Nicholas Carlson  1 , Thomas P Almdal  1   2 , Tobias Bomholt  1 , Christian Torp-Pedersen  3   4 , Kirsten Nørgaard  2   5 , Jesper H Svendsen  2   6 , Bo Feldt-Rasmussen  1   2 , Mads Hornum  1   2
Affiliations

The Association Between Hemoglobin A1c and Complications Among Individuals With Diabetes and Severe Chronic Kidney Disease

Dea H Kofod et al. Diabetes Care. .

Abstract

Objective: The optimal glycemic target for individuals with severe chronic kidney disease (CKD) remains unclear. We investigated the association between HbA1c and complications in individuals with diabetes and severe CKD.

Research design and methods: In a Danish nationwide registry-based cohort study, we included 27,113 individuals ≥18 years old with diabetes and severe CKD (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) between 2010 and 2022. As reference groups, we included an age- and sex-matched cohort of 80,131 individuals with diabetes and mild-to-moderate CKD (eGFR 30-59 mL/min/1.73 m2) and 80,797 individuals with diabetes and no-to-mild CKD (eGFR ≥60 mL/min/1.73 m2). Multiple Cox regressions were used to estimate the standardized 1-year risk of major adverse cardiovascular events (MACE), microvascular complications, and hospitalizations due to hypoglycemia across strata of HbA1c levels.

Results: For individuals with severe CKD, the risk of MACE significantly increased at HbA1c levels ≥7.2% (55 mmol/mol) (P < 0.01) and <5.8% (40 mmol/mol) (P < 0.001), compared with an HbA1c level of 6.3-6.6% (45-49 mmol/mol). The risk of microvascular complications significantly increased at HbA1c levels ≥7.2% (55 mmol/mol) (P < 0.001), and the risk of hospitalization due to hypoglycemia significantly increased at HbA1c levels ≥6.7% (50 mmol/mol) (P < 0.001). The association patterns between HbA1c and outcomes were similar in the severe CKD cohort compared with the matched cohorts with mild-to-moderate CKD and no-to-mild CKD.

Conclusions: Our data suggest an HbA1c range of 6.7-7.1% (50-54 mmol/mol) to be most favorable for reducing long-term complications in this high-risk population.

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Conflict of interest statement

Duality of Interest. D.H.K. has received speaker honoraria from Bayer outside the submitted work. T.P.A. owns stocks in Novo Nordisk. T.B. has served as an advisory board member for Medtronic and AstraZeneca; has been a speaker and lecturer for AstraZeneca and Boehringer Ingelheim; and has received research grant support from Novo Nordisk. K.N. serves as an advisor to Medtronic, Abbott, Convatec, and Novo Nordisk; owns shares in Novo Nordisk; has received research grants from Novo Nordisk, Zealand Pharma, Dexcom, and Medtronic to her institution; and received speaking fees from Medtronic and Novo Nordisk. J.H.S. serves on the advisory boards for Vital Beats and Medtronic and has received research grants from Medtronic outside this work. M.H. has served on scientific advisory boards for the following companies outside the scope of this study: Astra Zeneca, Novo Nordisk, Boehringer Ingelheim, GSK, and CSL Vifor Pharma; has served as a moderator of a symposium and an educational meeting for Astra Zeneca and Novo Nordisk; has received research grants from the A.P. Møller Foundation, Augustinus Foundation, Helen Bjørnow Foundation, and Lundbeck Foundation; and has received a Twinning Horizon 2020 Europe Grant. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Standardized 1-year risk with 95% CI for MACE (A), microvascular complications (B), and hospitalizations due to hypoglycemia (C) across strata of HbA1c in severe CKD and the matched cohorts.
Figure 2
Figure 2
Standardized 1-year risk with 95% CI for MACE, microvascular complications, and hospitalizations due to hypoglycemia in individuals with severe CKD stratified by sex (A), age (B), or diabetes type (C) across HbA1c categories.
See this image and copyright information in PMC

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