Comprehensive Glycomic Analysis Reveals that Human Serum Albumin Glycation Specifically Affects the Pharmacokinetics and Efficacy of Different Anticoagulant Drugs in Diabetes

Long-term hyperglycemia in diabetic patients leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in diabetic patients. In this study, a novel mass spectrometry (MS) approach was developed to reveal the differences in the profiles of HSA glycation sites between diabetic and healthy subjects. K199 was the glycation site most significantly changed in diabetic patients, contributing to different interactions of glycated HSA (gHSA) and normal HSA with two types of anticoagulant drugs, heparin and warfarin. In vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between diabetic and non-diabetic patients who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when administered anticoagulant drugs or drugs for treating other chronic diseases.