Association of continuous glucose monitoring metrics with early diabetic kidney disease in early-onset type 2 diabetes

Abstract

Background The rising prevalence of early-onset type 2 diabetes (T2DM) has become a major public health concern, with these patients facing a particularly high risk of early diabetic kidney disease (DKD). Although continuous glucose monitoring (CGM)-derived metrics have shown promise in predicting complications in later-onset T2DM, their utility in early-onset T2DM, a more aggressive phenotype characterized by rapid β-cell decline and heightened complication risk, remains unclear. Moreover, the relationship between glycemic variability and renal injury, as well as the mechanisms underlying the associations between CGM metrics and DKD, have not been fully elucidated. This study aimed to evaluate the associations of time in range (TIR), coefficient of variation (CV), and glycemic risk index (GRI) with early DKD in Chinese patients with early-onset T2DM, and to explore the potential mediating role of triglycerides. Methods This cross-sectional study included 810 individuals with early-onset T2DM, defined as diagnosis before age 40. All participants underwent ≥7 days of CGM. Early DKD was defined as a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m². Multivariable logistic regression, restricted cubic splines, and mediation analysis were used to evaluate independent associations, nonlinear relationships, and the mediating role of triglycerides (TG), respectively. Results Among the participants, 183 (22.59%) had early DKD. After full adjustment including HbA1c, higher TIR was associated with lower odds of early DKD (per 1% increase: OR 0.99, 95% CI 0.98–0.99, P < 0.001), whereas higher GRI was associated with increased odds (per 1-unit increase: OR 1.01, 95% CI 1.01–1.02, P < 0.001). A U-shaped relationship was observed between CV and early DKD risk, with the nadir observed at approximately 20–30% CV. In mediation analysis, TG statistically accounted for 13.01% of the association between TIR and early DKD, and 11.92% of the association between GRI and early DKD. Conclusions In Chinese patients with early-onset T2DM, CGM-derived metrics are independently associated with early DKD, with TIR and GRI showing opposite associations and CV exhibiting a U-shaped relationship. The observed association involving triglycerides suggests that lipid metabolism may be a correlate of glycemic control in relation to renal injury. These findings support a multidimensional strategy integrating glucose control, glycemic stability, and lipid management for renal protection in this high-risk population.