الفهرس 
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Abstract
DM a metabolic disorder characterized by elevated blood glucose levels due to defects in insulin secretion, insulin resistance, or both. The global prevalence of DM has been steadily increasing, with numbers rising from 108 million (4.7%) in 1980 to 425 million (8.5%) in 2017, projected to reach an estimated 629 million by 2045.
T2DM results from a complex interplay of genetic and environmental factors, including sedentary lifestyle and overweight. It can lead to the development of microvascular complications such as retinopathy, nephropathy, and neuropathy, as well as macrovascular complications like myocardial infarction, angina, stroke, and peripheral arterial disease (PAD).
Among the various complications, DN is the most prevalent cause of ESRD. Early histological signs of DN include thickening of the GBM and mesangial expansion, while an early ultrastructural feature involves the progressive loss of podocytes through apoptosis or detachment, detectable as podocyturia. Identifying these early changes is vital for the timely management and prevention of DKD.
DN is typically classified into five stages. The initial stage is characterized by renal hyperfiltration and hypertrophy, followed by a silent period devoid of clinical signs and symptoms in the second stage. The appearance of microalbuminuria occurs in the third stage, which can progress to macroalbuminuria in the fourth stage. The fifth stage is marked by a progressive and severe decline in renal function.
There is currently a lack of sensitive and specific biomarkers for the early detection and progression of DN, as well as the development of ESRD. Albuminuria has been widely used as a marker to monitor the onset and progression of DN. However, pathological abnormalities have been reported to occur even before the onset of microalbuminuria. Hence, the identification of new biomarkers capable of indicating early DN development and progression is crucial.
GPC5, belonging to the GPC family, is distinguished for its capacity to attach to the extracellular surface of the cell plasma membrane. This glypican member plays a vital role in the regulation of morphogens and growth factors during the process of development. The GPC5 gene is specifically located on chromosome 13q31.In addition to its developmental functions, GPC5 has been implicated in tumor progression, with its high expression promoting tumor cell proliferation and metastasis in certain cancers such as rhabdomyosarcoma and salivary adenoid cystic carcinoma.
GPC5 is predominantly expressed in podocytes of the kidney and is released in response to intraglomerular conditions. It enhances basic fibroblast growth factor 2 (FGF2) signaling, affects albumin permeability by influencing podocyte differentiation and function, and increases the vulnerability of the diabetic kidney to nephrotic damage. Podocytes, located on the urinary side of the GBM, make urine an appropriate source to search for markers of podocyte injury and quantification of podocyte damage in urinary sediment. However, assessing podocyte damage through urinary assays is challenging. Utilizing GPC5, a podocyte cell surface HSPG, may help overcome some of the limitations associated with previous urinary markers for DN.
The objective of our study was to investigate the urinary GPC5 levels as an early marker for DN in patients with T2DM. This cross-sectional study included participants aged 18 to 70 years. T2DM patients were selected based on WHO criteria, and individuals with DN were identified by urine albumin-to-creatinine ratio (ACR) falling within the range of microalbuminuria (30-300 mg/g) or macroalbuminuria (>300 mg/g).
The participants were divided into three groups:
1. group 1: 30 T2DM patients with DN, selected from the hospital.
2. group 2: 30 T2DM patients without DN, selected from the hospital.
3. group 3 (control group): 30 healthy individuals without DM, selected from the hospital.