Research Article: Glycemic burden-adjusted urinary glucose excretion deficit is associated with hyperuricemia in patients with type 2 diabetes
Abstract:
To investigate the associations of glycemic burden-adjusted urinary glucose excretion deficit (GB-UGE deficit) with serum uric acid levels and prevalent hyperuricemia in patients with type 2 diabetes mellitus (T2DM).
A total of 887 patients with T2DM were enrolled. GB-UGE deficit was defined as the inverse standardized residual from a linear regression of ln(urinary glucose excretion + 1) on glycated hemoglobin, fasting glucose, 2-hour postprandial glucose and eGFR; a higher GB-UGE deficit indicates less urinary glucose excretion than expected for a given glycemic burden. Participants were grouped by hyperuricemia status, with baseline demographic, metabolic and renal data collected. Statistical analyses included multiple linear regression, quartile-based logistic regression, stepwise-adjusted logistic regression, restricted cubic splines (RCS), ROC curves and sensitivity analyses.
Patients with hyperuricemia had a higher GB-UGE deficit ( P < 0.001 ). In the fully adjusted linear model, each 1-SD higher GB-UGE deficit was associated with a 15.44umol/L higher serum uric acid concentration (95% CI: 9.89 to 20.98, P < 0.001 ). RCS analysis demonstrated an overall association between GB-UGE deficit and serum uric acid ( P for overall association < 0.0001 ), with borderline evidence of nonlinearity ( P for nonlinearity = 0.0479 ); the association with prevalent hyperuricemia was approximately linear. Quartile analyses showed progressively higher odds of prevalent hyperuricemia ( P for trend < 0.001 ), and the sensitivity analyses produced estimates in the same direction. In the exploratory ROC analysis, the AUC increased by 0.021 from 0.787 for the conventional model to 0.808 for the model containing GB-UGE deficit ( DeLong P = 0.0014 ); however, the AUC increment between the UGE-containing model and the GB-UGE deficit model was merely 0.003 and lacked statistical significance.
In this single-center cross-sectional study of hospitalized T2DM patients, GB-UGE deficit was associated with elevated serum uric acid and prevalent hyperuricemia. As an exploratory cohort-specific residual index rather than a validated clinical marker, it may signal suboptimal urinary glucose excretion, with hypothetical links to disturbed renal tubular glucose and urate co-transport. Prospective multicenter external cohorts are required to verify its reproducibility, biological mechanism and translational value.
Introduction:
Hyperuricemia (HUA) is a metabolic disorder related to disturbed purine metabolism and is strongly associated with hypertension, insulin resistance, type 2 diabetes mellitus (T2DM), kidney disorders, and cardiovascular and cerebrovascular diseases ( 1 – 4 ). In patients with T2DM, HUA has been linked to diabetic microvascular complications, adverse cardiovascular outcomes, and all-cause mortality ( 5 – 10 ). Therefore, identifying metabolic characteristics and modifiable factors associated with serum uric acid in…
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