Glucokinase Regulatory Protein Gene Polymorphism as a Predictive Biomarker for Early Renal Injury in Newly Diagnosed Early‐Onset Type 2 Diabetes Mellitus

AIMS: Glucokinase regulatory protein gene (GCKR) polymorphisms have been linked to progressive renal dysfunction in diabetic populations. However, their role in early renal injury of diabetic kidney disease (DKD) remains unclear. This study aimed to investigate the association between GCKR genetic variants and early renal impairment in newly diagnosed early-onset type 2 diabetes mellitus (T2DM). METHODS: A total of 337 newly diagnosed early-onset T2DM patients from a prospective cohort were enroled. Baseline characteristics, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR) were collected. Seven single nucleotide polymorphisms (SNPs) in GCKR were genotyped using ASAMD microarrays. Participants were divided into normal (UACR < 30 mg/g) and elevated albuminuria (UACR ≥ 30 mg/g) groups. Logistic regression and multivariate linear regression were performed to evaluate the relationship between GCKR genotypes and UACR. RESULTS: , and median UACR was 14.97 mg/g; 107 patients (31.8%) presented with elevated UACR. Carriers of the GCKR rs1260326 T/T genotype exhibited significantly higher median UACR compared with C/T + C/C carriers (22.85 vs. 13.53 mg/g, p = 0.021). The rs1260326 T allele was independently associated with increased UACR under the additive genetic model (p = 0.003) adjusted for sex, age, body mass index (BMI), glycated haemoglobin (HbA1c), and systolic blood pressure (SBP). CONCLUSIONS: The GCKR rs1260326 T allele is independently associated with early renal injury in newly diagnosed early-onset T2DM. This genetic variant may serve as a predictive marker for early DKD risk stratification in this high-risk population.