#3938 THE ASSOCIATION BETWEEN HEMOGLOBIN A1C LEVEL AND COMPLICATIONS IN PATIENTS WITH DIABETES AND ADVANCED CHRONIC KIDNEY DISEASE
Authors: Kofod Dea , Carlson Nicholas , Bomholt Tobias , Almdal Thomas Peter , Svendsen Jesper , Gislason Gunnar , Torp Christian , Feldt-Rasmussen Bo , Hornum Mads 
Published: June 2023

Abstract

Background and Aims
Although the global prevalence of advanced diabetic kidney disease is increasing, the optimum glycemic target remains uncertain. Specifically, data pertaining to the association of hemoglobin A1c (HbA1c) level with micro- and macrovascular outcomes in patients with advanced diabetic kidney disease remain inconclusive. We examined the association between HbA1c levels and complications in patients with diabetes and chronic kidney disease (CKD) stage 4 and 5.

Method
In a Danish nationwide registry-based retrospective cohort study, we included persons ≥18 years of age with diabetes, an estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73m2 and a concurrent measured HbA1c between 2010 and 2022. Complications were categorized as 1) major adverse cardiovascular events (MACE) defined as a composite endpoint of acute myocardial infarction, stroke, and all-cause mortality; 2) microvascular complications defined as a composite endpoint of diabetic retinopathy, major lower extremity amputation, and start of dialysis; 3) hospitalization with hypoglycemia. Multiple outcome-specific Cox regressions stratified by HbA1c levels were performed to calculate the 1-year risk of complications standardized to the distribution of risk factors of all patients in the sample. The analyses regarding the risk of hypoglycemia were further stratified according to insulin treatment at baseline.

Results
In total, 34,046 patients were included. The median age was 76.2 (IQR 69.1-82.7) years and 54.6% were men. The median eGFR and HbA1c level was 26.4 (IQR 21.9-28.5) mL/min/1.73m2 and 53 (IQR 46-63) mmol/mol, respectively. Figure 1 depicts the 1-year risks of MACE and microvascular complications stratified by HbA1c level. We found a U-shaped association between HbA1c level and MACE where patients with an HbA1c level between 45-50 mmol/mol had the lowest risk. The risk increased significantly with an HbA1c level below 45 mmol/mol or above 65 mmol/mol compared with 45-50 mmol/mol (P&lt;0.001). The risk of microvascular complications was lowest at an HbA1c level between 35-40 mmol/mol. The risk increased significantly with increasing levels of HbA1c above 50 mmol/mol compared with 35-40 mmol/mol (P&lt;0.05). The 1-year risks of hospitalization with hypoglycemia stratified according to HbA1c level and insulin treatment are illustrated in Figure 2. For both groups, the risk was lowest at an HbA1c level between 30-40 mmol/mol and increased with increasing HbA1c levels.

Conclusion
In patients with diabetes and CKD stage 4 and 5, HbA1c levels &gt;65 mmol/mol and &lt;45 mmol/mol were associated with an increased risk of MACE, whereas HbA1c levels &gt;50 mmol/mol were associated with a higher risk of microvascular complications. Our findings suggest that appropriate glycemic control can reduce adverse outcomes in patients with advanced CKD without increasing the risk of hypoglycemia, but also suggest that intensive glycemic control (HbA1c &lt;45 mmol/mol) might be associated with an increased risk of MACE.