Endocrine Abstracts

Case History: A male in his 40’s diagnosed with type 2 diabetes in 2011 (BMI:20.7 kg/m²) was admitted with DKA (Dec 2018) after a period of poor glycaemic control on oral hypoglycaemic agents (Feb 2017: HbA1c-105 mmol/mol, Nov 2018: HbA1c-115 mmol/mol). There was dramatic improvement in glycaemic control after commencing him on subcutaneous insulin (April 2019: HbA1c-56 mmol/mol). GAD65 antibodies were positive (24 u/ml; normal<5 u/ml) and a diagnosis of latent autoimmune diabetes (LADA) was made. After the initiation of insulin and rapid improvement in glycaemic control, the patient began to experience severe debilitating “burning” and “shooting” pain (10/10) across his abdomen, back, thighs and shins with hyperalgesia and allodynia. On examination the patient had normal strength in all limbs (MRC power grading 5/5), no muscle wasting, and no clinical large fibre deficits. He had an irritable nociceptor phenotype with mechanical brush stroke allodynia.

Investigations: Nerve conduction studies were at the lower end of the normal range (sural/peroneal nerve conduction velocity/amplitude: 42.9 m/s; 7.5μV and 42.9 m/s; 3.9 m/s, respectively). MR brain imaging to rule out a central pain aetiology e.g. thalamic infarct was normal. However, corneal confocal microscopy (CCM), a measure of small sensory nerve fibre pathology was abnormal. Corneal nerve fibre length (CNFL) (6.0 mm/mm²), fibre density (CNFD) (12.9 /mm²) and branch density (CNBD) (6.7 /mm²) were all markedly reduced indicative of small fibre degeneration (normative values CNFL:>12.5 mm/mm², CNFD:>20.6 no/mm², CNBD:>22.7 no/mm²).

Results and treatment: A diagnosis of treatment-induced neuropathy of diabetes (insulin neuritis) due to rapid improvement in glycaemic control was made based on sudden onset of neuropathic pain and objective evidence of small fibre degeneration. He received multidisciplinary support in the form of maximal dose anti-neuropathic drug therapy, psychological therapy and physiotherapy. After nine months, there was a significant improvement in pain (3–4/10), CCM measures of small nerve fibres showed regeneration (CNFL: 13.1 mm/mm²; CNFD: 24.8 /mm²; CNBD: 18.7 /mm²) and he returned to work.

Conclusions and points for discussion: Treatment-induced neuropathy of diabetes is a potentially debilitating complication with an unknown prevalence. In contrast to diabetic polyneuropathy secondary to prolonged hyperglycaemia, treatment-induced neuropathy is self-limiting and will resolve with supportative treatment. Treatment-induced neuropathy should be considered as a differential diagnosis in cases of acute-onset neuropathic pain following initiation of therapy which rapidly improves glycaemic control.