Findings from a recent study published in BMC Ophthalmology elucidated the interrelationships between peripheral neuropathy, diabetic retinopathy (DR), and nephropathy in patients with type 2 diabetes mellitus (T2DM).
Give me some background.
Diabetic neuropathy, nephropathy, and retinopathy are major contributors to morbidity and diminished quality of life in patients with T2DM.
While these microvascular complications affect different organ systems, they share common pathophysiological mechanisms, such as:
- Chronic hyperglycemia-induced endothelial dysfunction
- Oxidative stress
- Inflammation
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Previous studies have suggested that the severity of one complication may correlate with or predict the presence or progression of others.
- For example: Worsening nephropathy has been linked to more severe DR.
As such, this study sought to evaluate how DR severity correlates with the presence and severity of diabetic neuropathy and nephropathy.
Now talk about the study.
This cross-sectional study was conducted at academic and medical centers affiliated with Shiraz University of Medical Sciences in Iran.
Investigators included adult patients (aged 18-75 years) with at least 5 years’ duration of T2DM and preserved renal function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2) in the analysis.
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DR was graded using the International Clinical DR Severity Scale and diabetic macular edema (DME) was assessed using spectral-domain optical coherence tomography (SD-OCT).
Peripheral neuropathy was quantified via nerve conduction studies (NCS)—specifically sural sensory nerve action (SNAP) amplitude—while nephropathy was evaluated by urinary albumin-to-creatinine ratio (UACR) and eGFR.
Findings?
In total, 155, 138, and 94 patients completed neuropathy, retinopathy, and nephropathy assessments, respectively.
Of the 138 participants who underwent fundus examination, 60% had proliferative DR (PDR) and 32% had DME.
Anything else?
A significant inverse correlation was identified between SNAP amplitude and both DR severity (p = 0.001) and DME presence (p = 0.001), indicating worse nerve conduction in advanced retinal disease.
- DME patients had a four-fold higher likelihood of impaired SNAP values (odds ratio [OR]: 4.0, 95% confidence interval [CI]: 1.849-8.653).
Moreover: DME presence was associated with significantly higher UACR (p = 0.011), and nephropathy severity demonstrated a mild but significant association with DR stage (p = 0.047).
Expert opinion?
The findings support earlier research that “macroalbuminuria strongly associates with sight-threatening DR, including PDR and DME, further supporting the interconnected nature of retinal and renal microvascular injury,” the study authors explained.
Further: The relationship between nephropathy and neuropathy reported in this study reinforced the results from a previous study, which found that elevated urinary albumin excretion correlated with more severe neuropathy.
- Note: Despite the smaller nephropathy sample size, this study still identified a significant association between nephropathy severity and neuropathy stage.
Any limitations?
A few … including:
- The cross-sectional study design prevented causal inference
- The tertiary care setting likely overrepresented cases of advanced DR and DME
- Nephropathy data were incomplete; however, comparative analysis showed no significant demographic or disease-severity differences between patients with and without urinary data, reducing the likelihood of selection bias
- Metabolic confounders—such as HbA1c, blood pressure, lipid profile, and smoking status—were not consistently available and could not be adjusted for, leaving room for residual confounding
Take home.
These findings suggest that the severity of DR and the presence of DME correlate strongly with peripheral neuropathy and increased albuminuria in T2DM patients, reflecting shared microvascular pathology.
For the future: OCT-based retinal findings, particularly DME, may serve as accessible clinical markers for identifying individuals at elevated risk of systemic microvascular complications.