In a recent study published online in the Journal of Diabetes Investigation, Jing Xu, MD, and Xinhe Zhou investigated the relationship between the serum uric acidto-high-density lipoprotein cholesterol ratio (UHR) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM), which had not been previously explored. Insulin resistance is a significant factor in various health conditions. While the hyperinsulinemiceuglycemic clamp is the gold standard for measuring it, this is not practical for routine clinical use. Thus, finding an accessible, costeffective diagnostic test for insulin resistance is crucial. “Uric acid can cause atherosclerosis and insulin resistance by reducing nitric oxide production, promoting vascular smooth muscle proliferation, and resulting in endothelial dysfunction,” Dr. Xu said. “Additionally, low levels of HDL-C play a role in the development of metabolic syndrome and insulin resistance.” The study included 2,545 patients with T2DM and measured insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR). The researchers calculated UHR as serum uric acid (UA) divided by high-density lipoprotein cholesterol (HDL-C) multiplied by 100. The study team conducted various statistical analyses to evaluate the association between UHR and IR, including Pearson correlation, multiple logistic regression, receiver operating characteristic (ROC) analysis, and subgroup analysis.
Higher UHR Linked With Increased IR
The findings revealed a positive correlation between UHR and HOMA-IR in both male and female patients with T2DM. Multiple logistic regression analysis confirmed that higher UHR levels were significantly associated with increased insulin resistance, even after adjusting for various factors. ROC analysis demonstrated that UHR had a larger area under the curve (AUC) compared with UA or HDL-C alone, indicating its potential as a better indicator of insulin resistance.
Subgroup analysis further revealed a more pronounced association between UHR and insulin resistance in patients with certain characteristics, such as a higher BMI, younger age, lower HbA1c levels, and absence of hypertension.
UHR’s Potential for Diagnosing IR
The study suggests that UHR could serve as a practical and novel biomarker for diagnosing IR in patients with T2DM. Previous research shows that hyperuricemia and low HDL-C levels are predictors of insulin resistance and T2DM. The mechanistic explanations for this association involve oxidative stress, impaired glucose uptake caused by elevated uric acid levels, and the protective effects of HDL-C on lipid metabolism.
While the study had strengths, including a large sample size and comprehensive statistical analyses, it also had limitations. It was a cross-sectional study, so researchers could not determine causal relationships. Additionally, the study population was limited to patients with T2DM, so the findings may not be generalizable to other populations.
“Our study provides strong evidence that UHR is positively correlated with an increase in HOMA-IR and the risk of IR in a mass of patients with T2DM,” said Dr Xu. “This relationship remains consistent regardless of gender, BMI, age, HbA1c, and history of hypertension. Notably, our ROC analysis demonstrates that UHR is more effective in detecting insulin resistance compared with UA or HDL-C alone, indicating that UHR is a specific and sensitive marker for insulin resistance.”
The study highlights the potential of UHR as a useful marker for identifying insulin resistance in patients with T2DM. Further research is needed to validate these findings and explore the clinical implications of using UHR in diagnosing and managing insulin resistance and related metabolic conditions
