Aug 2026· Journal of Visualized Experiments· Vol 234· 0 citations
Medicine
TL;DR
In patients with type 2 diabetes and preserved eGFR, hs-CRP and HOMA-IR were independently associated with markers of early renal impairment and suggest potential relevance for early risk characterization, although prospective studies are required to confirm clinical utility.
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.
Diabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM) and a leading cause of progressive renal failure worldwide. Although urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate remain the cornerstone measures for DKD assessment, simple and readily available biomarkers may provide complementary clinical information. In this cross-sectional study, 300 patients with T2DM were categorized into three groups according to UACR. The study evaluated and compared the triglyceride–glucose (TyG) index, neutrophil-to-lymphocyte ratio (NLR), and high-sensitivity C-reactive protein (hs-CRP) across albuminuria categories. All three biomarkers differed significantly among the albuminuria categories, with the highest levels observed in patients with macroalbuminuria. Receiver operating characteristic analyses demonstrated good discriminatory performance for albuminuria, with both NLR and hs-CRP exhibiting significantly greater discriminatory ability than the TyG index in several comparisons. In adjusted multinomial logistic regression analysis, NLR was independently associated with both microalbuminuria and macroalbuminuria, whereas the TyG index and hs-CRP were independently associated only with macroalbuminuria. These findings support the complementary role of these readily available biomarkers in the assessment of albuminuria in T2DM and provide a basis for future longitudinal studies to clarify their clinical significance.
Marwa M. Seyam, H. Elhabiby, Z. Hamed et al.· Scientific Reports· 0 citations
Background The uric acid to high-density lipoprotein cholesterol ratio (UHR), a composite biomarker integrating pro-inflammatory stress and vascular protection loss, has been linked to diabetic kidney disease (DKD) in cross-sectional studies, but longitudinal evidence on its association with continuous eGFR decline remains limited. Methods This retrospective cohort study included 8,827 community-managed type 2 diabetes patients from 54 health centers in Shenzhen, China, followed for 3 years (2023–2025). Baseline UHR was calculated as serum uric acid (μmol/L) divided by HDL-C (mmol/L). The primary outcome was annual eGFR slope, derived from individual linear regressions. Multivariable linear regression, restricted cubic spline analysis, model comparison, and pre-specified subgroup and sensitivity analyses were performed. Results In fully adjusted models, each 1-unit increase in baseline UHR was associated with greater annual eGFR decline (β = −0.002, 95% CI − 0.003 to −0.001, p = 0.002). In model comparison, UHR demonstrated a larger standardized effect (β = −0.052) than UA alone (β = −0.045) or HDL-C alone (β = 0.028) and achieved explanatory power comparable to the joint UA + HDL-C model with a lower AIC, indicating superior parsimony. Comparing extreme tertiles, the highest UHR tertile (T3) exhibited an additional 0.56 mL/min/1.73 m2/year decline versus the lowest (T1) (β = −0.558, p = 0.001; P for trend = 0.001), cumulating to 5.6 mL/min/1.73 m2 over 10 years. Truly negative eGFR slopes were more frequent in T3 (44.3%) than T1 (21.4%), and T3 had 34% higher odds of rapid eGFR decline (OR 1.34, 95% CI 1.11–1.61, p = 0.002). RCS analysis confirmed linearity (P for nonlinearity = 0.301). The association was stronger in patients aged >60 years and those with HbA1c ≥ 7% (P for interaction = 0.005 and <0.001) and remained robust in sensitivity analyses, including three-year average UHR (β = −0.009, p < 0.001). Conclusion Higher baseline UHR independently predicted faster eGFR decline in community-managed type 2 diabetes patients. As an inexpensive, readily available index, UHR may serve as a biomarker for identifying patients at elevated risk of progressive renal function loss.
Jian Yang, Ying Yi, Xiaoli Zhu et al.· Frontiers in Nutrition· 0 citations
Background: Diabetic kidney disease (DKD) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and represents a major cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Glycated hemoglobin (HbA1c) is an established biomarker of long-term glycemic control and is routinely used to assess glycemic status in patients with T2DM. However, the association between HbA1c levels and key indicators of renal function, particularly the urinary albumin-to-creatinine ratio (uACR) and estimated glomerular filtration rate (eGFR), remains incompletely characterized, particularly among Indian patients with T2DM. Evaluating these relationships may improve understanding of the association between long-term glycemic control and the development and progression of DKD in this population.
Methods: This cross-sectional observational study was conducted at a tertiary care center in Dehradun, India. A total of 100 patients with T2DM aged 35-70 years were enrolled. Clinical characteristics, HbA1c, uACR, eGFR, lipid profile, and comorbidities were assessed. Associations between HbA1c, uACR, and eGFR were analysed using descriptive statistics and correlation analysis. Multivariable binary logistic regression was performed to identify factors independently associated with reduced renal function, defined a priori as eGFR < 60 mL/min/1.73 m² (KDIGO Stage 3a or worse) at the time of the cross-sectional assessment.
Results: The mean age of participants was 55.2 ± 8.5 years, and 55% were male. Increasing HbA1c levels were significantly associated with higher uACR values and lower eGFR (both p<0.001). Mean uACR increased progressively from 32.1 ± 12.4 mg/g among patients with HbA1c <7% to 412.8 ± 102.6 mg/g among those with HbA1c >9%. Similarly, eGFR declined significantly with worsening glycemic control. Patients with macroalbuminuria demonstrated the highest HbA1c levels and the lowest eGFR values. Factors independently associated with reduced eGFR (< 60 mL/min/1.73 m²) in the cross-sectional multivariable model included HbA1c > 8% (adjusted OR 3.8, 95% CI 2.1–6.9), hypertension (aOR 2.9, 95% CI 1.8–4.7), current smoking (aOR 2.4, 95% CI 1.6–3.5), obesity (aOR 2.1, 95% CI 1.4–3.2), and age > 60 years (aOR 1.8, 95% CI 1.2–2.7).
Conclusions: Poor glycemic control is strongly associated with increased albuminuria and declining renal function in patients with T2DM. Routine monitoring of HbA1c, uACR, and eGFR may facilitate early identification of diabetic kidney disease. Prospective longitudinal studies are required to establish causality and to evaluate whether tighter glycaemic control reduces the risk of progression to renal impairment.
Key words: Type 2 Diabetes Mellitus; Glycated Hemoglobin (HbA1c); Urinary Albumin-Creatinine Ratio (uACR); Estimated Glomerular Filtration Rate (eGFR); Diabetic Kidney Disease.
Vivek Ruhela, Sahil Gupta, Alok Kumar· International Journal of Hea...· 0 citations
In patients with early-onset type 2 diabetes, an elevated TyG index was independently associated with increased UACR levels and served as a potential indicator for early diabetic kidney injury.
Wei Wang, Wenjing Dong, Shiju Yan et al.· BMC Endocrine Disorders· 0 citations
Background & Objectives: Diabetic kidney disease (DKD) is a major complication of type 2 diabetes mellitus (T2DM) leading to end-stage renal disease (ESRD). Early identification of declining renal function is vital to prevent disease progression. Estimated glomerular filtration rate (eGFR) calculated using serum creatinine or serum cystatin C serves as a key indicator of kidney function. This study aimed to compare creatinine-based (MDRD equation) and cystatin C-based (CKD-EPI 2012 equation) eGFR in relation to glycemic control (HbA1c) in patients with type 2 diabetes mellitus and healthy controls.Materials & Methods: This cross-sectional case–control study included 150 participants aged 25–70 years, comprising 75 clinically diagnosed T2DM patients (cases) and 75 apparently healthy individuals (controls). Patients with hypertension, known chronic kidney disease, hepatic/muscular disorders, or those undergoing dialysis were excluded. Serum creatinine (enzymatic method) and serum cystatin C (immunoturbidimetric assay) were analyzed on a Beckman AU5800 clinical chemistry analyzer. Glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography (HPLC). eGFR was calculated using the MDRD equation for creatinine and the 2012 CKD-EPI equation for cystatin C. Statistical analyses included independent Student’s t-test, paired t-test, Pearson’s correlation, and Receiver Operating Characteristic (ROC) curve analysis.Results: Mean HbA1c, serum creatinine, and serum cystatin C levels were significantly higher in T2DM cases than in healthy controls. Mean eGFR was significantly lower in diabetic patients compared to controls with both the MDRD equation (84.84 mL/min/1.73 m² vs. 98.07 mL/min/1.73 m²) and the CKD-EPI cystatin C equation (79.2 mL/min/1.73 m² vs. 90.35 mL/min/1.73 m²). A paired t-test demonstrated no statistically significant difference between eGFR calculated by MDRD and CKD-EPI (p = 0.318). Both eGFR estimates showed a significant inverse correlation with HbA1c (p < 0.05). ROC curve analysis showed excellent and comparable diagnostic performance for detecting early renal impairment (eGFR< 90 mL/min/1.73 m), with an area under the curve (AUC) of 0.95 (95% CI: 0.93–0.98) for creatinine-based eGFR and 0.96 (95% CI: 0.93–0.98) for cystatin C-based eGFR.Conclusion: Both creatinine-based (MDRD) and cystatin C-based (CKD-EPI) eGFR equations provide comparable clinical performance in evaluating renal function in patients with type 2 diabetes mellitus. Poorer glycemic control correlates with declining GFR, highlighting the value of early eGFR assessment alongside glycemic monitoring to identify individuals at risk of diabetic kidney disease.
Mariam Mahek Moizuddin, Jyotsna Volturi, Syeda Jaweria Omer· Indian Journal of Pharmaceut...· 0 citations
Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease and end-stage renal failure in patients with Type 2 Diabetes Mellitus (T2DM). This study evaluated the relationship between fasting serum cortisol levels and the severity of nephropathy and glycemic control in T2DM patients. A cross-sectional observational study was conducted over 18 months at a tertiary care center in Northern India. Among 500 screened patients, 100 individuals with T2DM and nephropathy (urinary albumin-creatinine ratio [UACR] ≥30 mg/g) were enrolled. Early morning fasting serum cortisol levels were measured using chemiluminescence immunoassay. Statistical analysis was performed using SPSS version 26. The mean age of participants was 60.7±11.25 years and 93% had diabetes for more than five years. Serum cortisol levels were significantly higher in patients with poor glycemic control (HbA1c >10%) compared with those having HbA1c 6.5–8% (24.05±3.43 vs. 22.46±2.12 µg/dL; p=0.019). Patients with macroalbuminuria showed significantly higher cortisol levels than those with microalbuminuria (24.45±3.02 vs. 21.47±1.84 µg/dL; p=0.001). Cortisol demonstrated positive correlations with UACR (r=0.425), diabetes duration (r=0.412) and HbA1c (r=0.385) (all p<0.001). Higher cortisol levels were also associated with diabetic retinopathy and neuropathy. Elevated serum cortisol levels are associated with poor glycemic control, increasing albuminuria and microvascular complications in T2DM. Serum cortisol may serve as a useful biomarker for identifying patients at risk of progressive diabetic nephropathy.
Akash Bawa, Raman Sharma, Jasmine Kaur et al.· International Research Journ...· 0 citations
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