Serum uric acid is independently associated with diabetic nephropathy but not diabetic retinopathy in patients with type 2 diabetes mellitus

Abstract

Background: This study aims to investigate the relationship between serum uric acid (SUA) and the severity of diabetic nephropathy (DN) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 2961 patients were enrolled in the present cross-sectional study. The severity of DN was determined by 24-hour urinary albumin excretion (UAE), which was classified as normal (UAE <30 mg/24 h), microalbuminuria (UAE: 30-299 mg/24 h), and macroalbuminuria (≥300 mg/24 h). The severity of DR was determined by non–mydriatic retinal photography and was classified as non–diabetic retinopathy (NDR), non–proliferative diabetic retinopathy (NPDR), and proliferative DR (PDR). Results: Patients with high SUA levels (≥420 μmol/L for males and ≥360 μmol/L for females) had a significantly higher prevalence of DN (UAE ≥30 mg/24 h, 39.3% vs 26.3%; p < 0.001), higher UAE levels (140 ± 297 vs 63 ± 175 mg/24 h; p < 0.001), and lower estimated glomerular filtration rate (eGFR; 79.3 ± 26.8 vs 96.8 ± 19.6 mL/min/1.73 m2; p < 0.001), when compared with patients with normal SUA levels. However, the prevalence of DR, NPDR, or PDR did not differ. Furthermore, the concentration of SUA was higher in patients with higher severity of DN (all, p < 0.001) and patients with PDR (compared with NDR or NPDR, p < 0.05). SUA levels were positively associated with male gender, body mass index, the use of diuretics, triglyceride, low-density lipoprotein, and UAE levels, whereas they were negatively correlated with high-density lipoprotein, fasting blood glucose, glycosylated hemoglobin, and eGFR. After adjustment, SUA remained significantly associated with UAE (r = 0.069, p < 0.001). Conclusion: For patients with T2DM, higher SUA levels are associated with higher UAE, lower eGFR, and higher prevalence of DN, but not DR.

Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients

“…In patients with T2D, patients with PDR have higher levels of SUA than those without DR or with NPDR. 21,22 Furthermore, a large-scale prospective study of 749 patients with T2D revealed that SUA levels were associated with a worsening in the severity of DR in Taiwan. 12 Moreover, intravitreal levels of UA were significantly higher in diabetic patients with macular edema than in nondiabetic control subjects.…”

Supplemental Information 2: Raw data

“…In contrast to DN, neither DR nor DPN was found associated with SUA levels, which was consistent with the previous reports (Xia et al, 2020). On the contrary, a multicenter cross-sectional study in Thailand concludes that SUA is independently associated with peripheral neuropathy in T2DM patients, and elevated SUA should be considered a risk factor for DPN in clinical practice (Kaewput et al, 2020).Two explanations are suggested for the controversial findings.…”

Correlation between serum C-peptide-releasing effects and the risk of elevated uric acid in type 2 diabetes mellitus

“…Elevated SUA levels are independently correlated with the incidences of hypertension and metabolic syndrome (MetS) in some Asian countries including China, Japan, and Korea [2][3][4][5]. For patients with type 2 diabetes mellitus (T2DM), higher SUA levels are associated with the lower estimated glomerular filtration rate (eGFR) and higher prevalence of diabetic nephropathy, but not diabetic retinopathy [6]. Moreover, in general, the decline in SUA levels slows the progression of diabetic kidney disease [7].…”