Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes

Treatment-induced neuropathy in diabetes (also referred to as insulin neuritis) is considered a rare iatrogenic small fibre neuropathy caused by an abrupt improvement in glycaemic control in the setting of chronic hyperglycaemia. The prevalence and risk factors of this disorder are not known. In a retrospective review of all individuals referred to a tertiary care diabetic neuropathy clinic over 5 years, we define the proportion of individuals that present with and the risk factors for development of treatment-induced neuropathy in diabetes. Nine hundred and fifty-four individuals were evaluated for a possible diabetic neuropathy. Treatment-induced neuropathy in diabetes was defined as the acute onset of neuropathic pain and/or autonomic dysfunction within 8 weeks of a large improvement in glycaemic control-specified as a decrease in glycosylated haemoglobin A1C (HbA1c) of ≥2% points over 3 months. Detailed structured neurologic examinations, glucose control logs, pain scores, autonomic symptoms and other microvascular complications were measured every 3-6 months for the duration of follow-up. Of 954 patients evaluated for diabetic neuropathy, 104/954 subjects (10.9%) met criteria for treatment-induced neuropathy in diabetes with an acute increase in neuropathic or autonomic symptoms or signs coinciding with a substantial decrease in HbA1c. Individuals with a decrease in HbA1c had a much greater risk of developing a painful or autonomic neuropathy than those individuals with no change in HbA1c (P < 0.001), but also had a higher risk of developing retinopathy (P < 0.001) and microalbuminuria (P < 0.001). There was a strong correlation between the magnitude of decrease in HbA1c, the severity of neuropathic pain (R = 0.84, P < 0.001), the degree of parasympathetic dysfunction (R = -0.52, P < 0.01) and impairment of sympathetic adrenergic function as measured by fall in blood pressure on tilt-table testing (R = -0.63, P < 0.001). With a decrease in HbA1c of 2-3% points over 3 months there was a 20% absolute risk of developing treatment-induced neuropathy in diabetes, with a decrease in HbA1c of >4% points over 3 months the absolute risk of developing treatment-induced neuropathy in diabetes exceeded 80%. Treatment-induced neuropathy of diabetes is an underestimated iatrogenic disorder associated with diffuse microvascular complications. Rapid glycaemic change in patients with uncontrolled diabetes increases the risk of this complication.