Associations of Serum High-Sensitivity C-Reactive Protein (hs-CRP) And Insulin Resistance With Early Renal Impairment In Type 2 Diabetes

Summary

In a retrospective cross-sectional study of 126 patients with type 2 diabetes and preserved eGFR, hs-CRP in the overall sample and HOMA-IR in the subgroup without exogenous insulin were independently associated with ln-UACR, showed dose-response patterns, and remained consistent in sensitivity analyses. This suggests possible relevance to early renal risk assessment.

Abstract

Early diabetic kidney disease in type 2 diabetes is characterized by increased urinary albumin excretion despite preserved estimated glomerular filtration rate (eGFR). The roles of systemic inflammation and insulin resistance at this stage remain incompletely defined. This study evaluated the associations of high-sensitivity C-reactive protein (hs-CRP) and insulin resistance (HOMA-IR) with early renal impairment. In this single-center retrospective cross-sectional study, 126 patients with type 2 diabetes and eGFR ≥60 mL/min/1.73 m² were included; patients not using exogenous insulin formed a subgroup (n=97). The primary outcome was natural log-transformed urine albumin-to-creatinine ratio (ln-UACR). Associations were assessed using Spearman correlation and multivariable linear regression adjusted for age, sex, diabetes duration, systolic blood pressure, and glycated hemoglobin (HbA1c). Dose-response relationships, joint exposure effects, surrogate outcomes, and sensitivity analyses were also examined. Statistical analyses were performed using R (version 4.3.2). ln-UACR was positively correlated with hs-CRP in the overall sample (ρ=0.28, p=0.001) and with HOMA-IR in the subgroup (ρ=0.26, p=0.009). After adjustment, hs-CRP remained associated with ln-UACR in both the overall sample (βstd=0.23) and subgroup (βstd=0.22), and HOMA-IR remained associated in the subgroup (βstd=0.17, p=0.018). ln-UACR increased across tertiles of both exposures (p for trend <0.01). The high hs-CRP/high HOMA-IR group showed higher ln-UACR compared with the low/low group (mean difference 0.64, 95% CI 0.37–0.88), without significant interaction (p=0.173). Associations were consistent across surrogate outcomes and sensitivity analyses. In patients with type 2 diabetes and preserved eGFR, hs-CRP and HOMA-IR were independently associated with markers of early renal impairment. These findings suggest potential relevance for early risk characterization, although prospective studies are required to confirm clinical utility.

Introduction

Diabetic kidney disease is one of the most common chronic complications of type 2 diabetes¹. In its early stage, increased urinary albumin excretion is often present while estimated glomerular filtration rate (eGFR) remains preserved; with disease progression, eGFR declines and the risks of cardiovascular events and death increase substantially². However, significant early detection gaps exist in clinical practice. Currently available routine tests (including serum creatinine and eGFR) may underestimate early renal injury before a measurable drop in eGFR, thereby lacking sensitivity for early structural damage. While the....

Protocol

This retrospective study was reviewed and approved by the Medical Ethics Committee of Baoquanling Hospital of Beidahuang Group on May 9, 2025 (Approval No. BQH-BDHG-EC-2025-056), and informed consent was waived. The study was conducted in accordance with the Declaration of Helsinki and the hospital's data privacy management policy, and all personally identifiable information was de-identified before analysis. The research tools used in this study are listed in the Table of Materials.

1. Study design

This was a single-center retrospective cross-sectional study conducted in the D....

Results

Study population and baseline characteristics

A total of 467 patients with type 2 diabetes were screened. After exclusion of records with missing key laboratory tests, eGFR < 60 mL/min/1.73 m², acute infection/inflammation or contaminated urine tests, macroalbuminuria, and other prespecified comorbid conditions, 126 patients were included in the final analytical sample. Among these, 97 patients not using exogenous insulin comprised the HOMA-IR subgroup (

Discussion

In the type 2 diabetes population with preserved eGFR, elevated hs-CRP levels were consistently associated with increased urinary albumin excretion and remained independently associated after adjustment for age, sex, diabetes duration, SBP, and HbA1c. When hs-CRP increased by quantiles, the adjusted mean of ln-UACR increased linearly, suggesting that this association has a gradient feature. As a sensitive indicator of low-grade systemic inflammation, hs-CRP may reflect the immune activation state under metabolic stress

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Electronic medical record system (EMR)	N/A	N/A	Institutional electronic medical record system used to extract demographic, clinical, comorbidity, blood pressure, and medication data.
Laboratory information system (LIS)	N/A	N/A	Institutional laboratory information system used to extract hs-CRP, FPG, FINS, HbA1c, urine albumin, urine creatinine, and serum creatinine results.
General laboratory analyzers	Roche Diagnostics	N/A	Used to measure general laboratory indicators.
Immunoassay System	Roche Diagnostics, Germany	Roche Cobas c702 automatic biochemical analyzer	Used to measure hs-CRP, FPG, urine albumin, urine creatinine, and serum creatinine.
High-performance liquid chromatography analyzer	Trinity Biotech	N/A	Lon-exchange high-performance liquid chromatography  for glycated hemoglobin measurement.
Automated electronic blood pressure monitor	Omron	Omron HBP-9020	Used to measure systolic and diastolic blood pressure  at 1-min intervals after 5 min of rest. The first reading was discarded, and the average of the second and third measures was recorded as the index blood pressure value.
R (version 4.3.2)	R Foundation for Statistical Computing	N/A	Statistical analysis software; packages used: stats, car, sandwich, lmtest, mice, ggplot2.