Metabolic crosstalk and therapeutic interplay between diabetes and hyperuricemia

Abstract

Hyperuricemia and diabetes mellitus (DM) are prevalent metabolic disorders with high comorbidity, imposing a substantial global public health burden. Their coexistence is not merely additive but synergistic, exacerbating metabolic dysregulation through mechanisms such as insulin resistance and β-cell apoptosis, ultimately establishing a vicious cycle. Both disorders induce acute and chronic damage to vital organs, particularly the cardiovascular, renal systems. Hyperuricemia aggravates diabetic complications, notably diabetic cardiomyopathy, nephropathy and retinopathy via oxidative stress, inflammation, and metabolic dysregulation. Current urate-lowering therapies (ULTs), such as xanthine oxidase inhibitors and urate transporter 1 (URAT1, also known as SLC22A12) antagonists, demonstrate potential benefits in ameliorating diabetic complications but face challenges including safety concerns and dose adjustments. Similarly, several glucose-lowering drugs also exhibit the benefits of improving hyperuricemia. This review summarizes the metabolic crosstalk and therapeutic interplay between hyperuricemia and DM, examines the pathogenic role of uric acid in diabetic complications, and discusses the benefits and challenges of existing ULTs and glucose-lowering drugs in disrupting this cycle of metabolic dysregulation and concurrent organ damage. We hope our findings deepen the comprehension of the intricate metabolic crosstalk between glucose and urate homeostasis, providing novel therapeutic insights for patients with comorbid DM and hyperuricemia.