Written by Kevin Liu
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In Danish patients with diabetes and chronic kidney disease (CKD), very low (A1c < 5.8) and very high (A1C > 8.0) HbA1c levels were linked to worse outcomes.
Goldilock’s phenomenon for A1c and CKD: HbA1c of 6.3-7.1% is just right
Glycemic control in diabetes with chronic kidney disease has some uncertainty, with guidelines recommending HbA1c goals < 7%, while recent studies of CKD patients recommended HbA1c goals between 7-8%.
In this large population-based retrospective cohort analysis of 27,113 adults in Denmark between 2010-2022, researchers compared the association between HbA1c levels and composite outcomes, including major adverse cardiovascular events (MACE), microvascular complications, and hospitalizations due to hypoglycemia. HbA1c levels were risk stratified by severity of CKD (severe, eGFR < 30; mild-moderate, eGFR 30-59; no-to-mild, eGFR ≥ 60). For patients with severe CKD, the risk of MACE increased significantly at HbA1c levels <5.8% and ≥7.2%, compared with an HbA1c level of 6.3–6.6% (45-49 mmol/mol). The risk of microvascular complications increased significantly at HbA1c levels ≥7.2%, whereas there was no statistically significant difference at HbA1c levels ranging from 4.9% to 7.1%. Finally, the risk of hospitalization due to hypoglycemia was lowest for individuals with an HbA1c level of 5.8-6.2%, and significantly increased with increasing HbA1c levels ≥6.7%. The association between HbA1c levels and outcomes in the severe CKD followed a similar pattern to that observed in the mild-moderate and no-to-mild CKD cohorts. These findings persisted across age, sex, insulin use, and comorbid subgroups.
How does this change my practice?
This study affirms that a HbA1c between 6.7-7.1% in patients with severe CKD is the goal. MACE events increased below an A1C of 5.8% regardless of CKD status, and paradoxically, patients with a higher A1c were more likely to experience hypoglycemic episodes. I have struggled at times to counsel younger, ambitious patients aiming to return to a sub-diabetic A1c of < 5%, and this study presents concrete evidence and quantifies the increased risk of aiming too aggressively. Like Goldilocks and the three bears, only an A1c of 6.7-7.1% is just right.
Source
The Association Between Hemoglobin A1c and Complications Among Individuals With Diabetes and Severe Chronic Kidney Disease. Diabetes Care. 2025 Jun 7:dc250339. doi: 10.2337/dc25-0339. Epub ahead of print. PMID: 40481664
