The association between hemoglobin A1c and complications among individuals with diabetes and severe chronic kidney disease

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 in-cluded 27,113 individuals ≥18 years old with diabetes and severe CKD (estimated glomeru-lar 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), com-pared to an HbA1c level of 6.3–6.6% (45–49 mmol/mol). The risk of microvascular compli-cations 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 to 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.