Diabetic neuropathic cachexia is an acute complication of diabetes marked by such extreme pain and weight loss that, although exceptionally rare, it imparts major challenges in management and diagnosis. Little is known of the fundamental pathophysiologic features of the peripheral nervous system in this condition; for example, the symptomatic resolution that is classically observed may arise from either complete destruction of pain-transmitting nerve fibers or from their repair. To reconcile this issue, we report the first case to our knowledge that the nerve dysfunction is reversible. A 36-year-old woman presented with subacute hyperglycemic symptoms. Soon after initiation of insulin therapy and the decline of HbA1c from 14.9 to 5.5%, she developed severe lancinating pain and profound weight loss associated with anorexia, amenorrhea, insomnia, and dehydration. On examination, allodynia was so pronounced that a light touch to her shoulder would cause her to weep. Profound loss of subcutaneous adipose tissue and loss of muscle bulk was evident, such that her weight had decreased from a baseline of 58.3 to 41.8 kg (corresponding to a decrease in BMI from 21 to 15.7 kg/m2). Pain, temperature, and light touch sensation were abnormal in the hands and feet.
Blood count, chemistries, and thyroid and cortisol levels were normal. Further tests for malignancy and malabsorption, including serum immunoelectrophoresis, computed tomography, bone scan, and endoscopy with biopsies, were normal. Titers for antinuclear antibodies and viral etiologies were negative. Nerve conduction studies demonstrated impaired conduction velocity (indicative of impaired myelin sheath function) and impaired amplitude potentials (indicative of impaired nerve axon function) of both sensory and motor nerves.
Hydration, oral nutritional support, and opiate therapy were provided during an 8-week hospitalization. She subsequently received symptomatic therapy with amitriptyline and gabapentin; a year later these analgesic therapies were discontinued, and her weight had returned to baseline. The aberrations in nerve function had normalized; most dramatic was the improvement in nerve axon function, represented by a doubling of amplitude potentials. For example, in the sural nerve the conduction velocity improved by 30% (from 36 to 47 m/s) and the sensory amplitude potentials doubled (from 3.4 to 7.5 μV) from baseline. Similar changes were seen in the median and peroneal nerves for these parameters and also for F-wave latencies and vibration perception thresholds.
The profound weight loss, the symmetrical sensorimotor polyneuropathy associated with dramatic painful paresthesias devoid of weakness, the temporal relation with insulin therapy, and the chronic course are in complete accordance with the diagnosis of diabetic neuropathic cachexia (1). This report emphasizes the need for vigilant symptomatic therapy of diabetic neuropathic cachexia while expediting investigations for eliminating alternate causes. Unique to this report, however, is the objective finding of nerve dysfunction that was dramatically reversed after symptomatic recovery; it supports the proposed hypothesis that paradoxical hypoxic injury occurs at the initiation of insulin therapy (2, 3). This case fundamentally suggests that the reversal of painful symptoms is associated with repair of functional aberrations in nerve fibers induced by hypoxia rather than their irreversible ischemic destruction.