A recent case report of a young type 1 diabetic man published in the British Medical Journal is a reminder of an important clinical finding and a picture of what may be more common than previously thought....
A 32-year-old man presented himself with sudden onset of severe lower limb pain that showed marked progression and was refractory to analgesic and muscle relaxant therapies. It became so severe that the patient could no longer stand. The patient's medical history included type 1 diabetes diagnosed three years ago and deep vein thrombosis in the left leg four years ago.
In addition to an extensive diagnostic work-up, he was tried on various analgesics - without any improvement. After careful review of his medical records, a significant decrease in his HbA1c level 6 months before the onset of symptoms was noted.
He was then diagnosed with treatment-induced neuropathy in diabetes mellitus (TIND), formerly also known as "insulin neuritis".1
This is an acute, painful and autonomic neuropathy that can develop when glycosylated haemoglobin (HbA1c) is rapidly lowered in patients with long-standing diabetes mellitus. It is associated with burning and shooting pain and sometimes orthostatic hypotension with syncope.2
A retrospective study analysing data from 910 patients a few years ago suggested that treatment-induced neuropathy is more common in diabetes than previously thought and that its occurrence is strongly dependent on the speed of HbA1c reduction.3 Of 168 patients whose HbA1c was lowered by more than two percentage points within three months, 104 (10.9%) suffered this complication. Among patients with slower HbA1c adjustment, this occurred less than half as often (4.3%). If the HbA1c was lowered by four percentage points within three months, as many as 80% of patients suffered treatment-induced neuropathy. Almost all of those affected had previously experienced neuropathic symptoms only to a small extent or not at all. Weight loss emerged as an additional risk factor.2
Possible pathophysiological mechanisms include endoneural oedema developing from the opening of epineural arterio-venous shunts, apoptosis from glucose deprivation or microvascular neuronal damage. The additional risk factor of weight loss suggests a possible association with vitamin deficiency or an increase in proinflammatory cytokines.
In contrast, which drug had been used for glycaemic control seemed to be irrelevant for the risk of TIND.2
Symptomatic therapy is recommended and usually symptoms improve over time.
Our patient from the case outlined at the beginning was treated with amitriptyline and showed significant improvement after the first month.
References:
1. Ferreira, M., Camoes, G., Gomes, J. F. de F. & Ferreira, D. M. Treatment-induced diabetes neuropathy: reminder of an important clinical lesson. BMJ Case Reports CP 14, e241849 (2021).
2. Sommer, C. Häufiger als bisher angenommen? InFo Neurologie 17, 22–22 (2015). (English title: More common than previously thought?)
3. Gibbons, C. H. & Freeman, R. Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes. Brain 138, 43–52 (2015).