Urinary Fetuin-A with Specific Post-Translational Modification in Type 1 Diabetes Patients with Normoalbuminuria and Preserved Kidney Function

TL;DR

This study explores a modified form of fetuin-A in urine as a potential early marker of kidney dysfunction in male type 1 diabetes patients.

Contribution

The study introduces a sex-specific association between a modified fetuin-A peptide and early kidney dysfunction in type 1 diabetes.

Findings

uPTM3-FetA levels were not significantly different between normal and declining kidney function groups overall.

Male T1D patients with lower eGFR had significantly higher uPTM3-FetA excretion compared to those with higher eGFR.

BMI, hs-CRP, resistin, and HDL-cholesterol were independent predictors of uPTM3-FetA excretion.

Abstract

Background/Objectives: Post-translationally modified peptide fragments of fetuin-A (FetA) were identified as a potential biomarker of diabetic kidney disease (DKD). An independent association between urinary FetA-derived peptide levels (uPTM3-FetA) and DKD progression in patients with type 2 diabetes (T2D) was evidenced. This study aimed to explore uPTM3-FetA excretion and its associations with insulin resistance, inflammatory and metabolic biomarkers in patients with type 1 diabetes (T1D), and the normal albuminuria and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2. Methods: uPTM3-FetA levels in aliquots of 24 h urine specimens, routine laboratory renal, metabolic and inflammatory tests, adipokines (leptin, adiponectin, resistin), and insulin resistance, assessed as the estimated glucose disposal rate (eGDR), were measured in a cohort of 169 adult T1D patients. To evaluate the changes in early renal dysfunction, the cohort was divided according to the median eGFR. Above- and below-median-eGFR groups were considered as having normal and declining kidney function, respectively. Results: The median (IQR) uPTM3-FetA level was 11.7 (8.43–16.65 µg/24 h), with no significant difference between males and females, as well as normal and declining kidney function patients. However, a sex-specific analysis revealed a significantly higher uPTM3-FetA excretion in male T1D patients with lower eGFRs, when compared to those with higher eGFRs, whereas no such difference was observed in female patients. BMI, hs-CRP, resistin and HDL-cholesterol were identified as independent predictors of uPTM3-FetA excretion. Conclusions: Our results implicate the potential role of uPTM3-FetA in the detection of an early renal dysfunction in male patients with T1DM and pinpoint the importance of a sex-specific approach in diabetes diagnostics and research.

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