Diabetic Neuropathy Assessment and Management

Diabetic neuropathy encompasses a spectrum of nerve disorders caused by chronic hyperglycaemia and metabolic dysregulation in patients with type 1 and type 2 diabetes. The most prevalent form is distal symmetric polyneuropathy, characterised by length-dependent axonal degeneration affecting sensory, motor and autonomic fibres. Early identification relies on clinical screening (including symptom questionnaires and neurological examination), quantitative sensory testing and electrophysiological studies. Advances in non-invasive imaging such as corneal confocal microscopy and skin biopsy assessment of intra-epidermal nerve fibre density provide objective measures of small-fibre damage. Management strategies combine tight glycaemic control, lifestyle interventions and pathogenetic treatments targeting oxidative stress, inflammation and mitochondrial dysfunction. Symptomatic relief of neuropathic pain employs antidepressants, anticonvulsants and topical agents, with growing emphasis on individualised, phenotype-driven therapy. Research efforts increasingly aim to translate mechanistic insights into disease-modifying approaches and to refine risk stratification for early intervention.

Research from Nature Portfolio

A recent study in a Drosophila model has illuminated the role of the deubiquitinase UCHL1 in linking insulin resistance and diabetic sensory neuropathy. Loss of UCHL1 in sensory neurons induced features of type 2 diabetes and axonal degeneration, while overexpression of UCHL1 ameliorated these defects. Mechanistically, UCHL1 modulates the ubiquitination status of insulin receptor substrate 1 by antagonising an E3 ligase, Cullin 1, and pharmacological inhibition of Cullin 1 activity restored normal insulin signalling and nerve function. These findings offer a novel molecular target for therapeutic development aimed at both metabolic regulation and neuroprotection in diabetic neuropathy.

Diabetic Neuropathy Assessment and Management publication trend

The graph below shows the total number of articles in diabetic neuropathy assessment and management across all publications each year (not limited to Nature Index journals).

Technical terms

Distal symmetric polyneuropathy: A form of diabetic neuropathy in which nerve damage begins in the longest peripheral nerves, producing symmetrical sensory and motor symptoms in the feet and hands.

Quantitative sensory testing (QST): A psychophysical method to assess sensory nerve function by measuring detection thresholds for temperature and vibration stimuli.

Corneal confocal microscopy (CCM): A non-invasive imaging technique that visualises and quantifies small nerve fibres in the cornea as a surrogate for peripheral small-fibre neuropathy.

Intra-epidermal nerve fibre density (IENFD): A histological measure of small-fibre abundance in skin biopsies, reflecting peripheral nerve fibre integrity.

Ubiquitin C-terminal hydrolase L1 (UCHL1): A neuronal deubiquitinating enzyme that regulates protein turnover and has emerged as a mediator of insulin signalling and axonal maintenance in diabetic sensory neurons.

References

1. Diabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila. Nature Communications (2024).
2. Spectrum of Diabetic Neuropathy: New Insights in Diagnosis and Treatment. Annual Review of Medicine (2024).
3. New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain. Neuron (2017).
4. Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy. PLOS ONE (2017).
5. Painful and Painless Diabetic Neuropathies: What Is the Difference?. Current Diabetes Reports (2019).