Rare case of diabetic neuropathic cachexia along with diabetic amyotrophy

Background

Diabetic neuropathic cachexia (DNC) is associated with poor glycaemic control and is reversible over weeks to months. This was first reported by Ellenberg and the classic hallmark of DNC consists of varying degrees of symmetrical painful sensory and motor peripheral neuropathy.1 These patients may also have autonomic neuropathy symptoms such as gastroparesis, altered bowel habit, orthostatism and impotence.1 Patients also have reports of anorexia, emaciation of fat and lean muscle mass and may report of emotional instability.2 One case study reported the same patient to have DNC two times due to poorly controlled diabetes, which improved with adequate glycaemic control.3 Hence, it is important to identify this problem early and the clinical features can be reversed within a few months if appropriate treatment is initiated.

Case presentation

This 65-year-old patient had a previous medical history of gunshot wounds 40 years ago in both legs and alcohol excess for 20–25 years. He developed symptoms of daytime and nocturnal polyuria and polydipsia at the beginning of 2020. Following this, he noticed symptoms of tingling, numbness and cold sensation in his feet over the next few months. He also reported of weight loss for 3–4 months prior to his diagnosis with diabetes. He could not get an outpatient hospital appointment due to COVID-19 and saw his GP a few times for his symptoms during this period. He was formally diagnosed as having type 2 diabetes mellitus by his GP in July 2020 and was commenced on gliclazide and metformin. He subsequently developed symptoms of night sweats, dizziness, altered bowel habit (predominantly constipation), anorexia and had lost approximately 4.5 kg weight over the preceding 6 months. These symptoms adversely affected his quality of life, including his mood and sleep.

He was then referred to diabetes specialist nurse who added empaglaflozin and alogliptin in August. His symptoms continued to get worse and his partner brought him to his local hospital emergency department. He was noted to have generalised muscle wasting and dorsal guttering in both hands due to profound muscle wasting (figures 1 and 2). His power was 2/5 in the left lower limb and 4/5 in the right lower limb. His ankle reflexes were bilaterally diminished and plantar reflexes were equivocal. His right knee jerk was intact but was absent on the left side. His coordination was intact on the right side but was unable to fully assess the left side, due to weakness. He was also noted to have glove and stocking distribution of sensory impairment.

His blood showed elevated HbA1c 124 mmol/mol; however, his renal function, thyroid function, vitamin B12, folate and ferritin were normal. His blood glucose was 22.0 on admission. His autoimmune screen including coeliac screen was negative. His CT thorax/abdomen/pelvis (TAP) and CT lumbar spine revealed no structural bony lesion.

He was admitted to the metabolic ward under the endocrinology team. Insulin NovoMix 30 was commenced at 30 units two times per day dosing. The patient was reviewed by Neurology consultant during admission and had nerve conduction studies (NCS) that confirmed the presence of peripheral sensory motor neuropathy. This was deemed to be due to poorly controlled diabetes after exclusion of other causes. He was discharged with outpatient follow-up.

He was reviewed in diabetes clinic after 3 months and his weight had improved from 43 to 53 kg, he had also made a significant improvement in symptoms. His HbA1c had reduced to 50 mmol/mol and his insulin dose was titrated accordingly to 24 units two times per day.

Differential diagnosis

The common differential diagnosis includes chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which has an insidious onset and is a progressive or relapsing symmetric sensorimotor disorder. It includes weakness of both proximal and distal limbs and motor symptoms are predominant. Sensory impairment is usually greater for vibration and position sense than for pain and temperature sense.

Autonomic symptoms are very mild. Another common feature in these patients is intention tremor and gait ataxia. NCS studies show peripheral nerve demyelination; however, there was no evidence of demyelination on NCS and no other common features of CIDP were present in this patient. Furthermore, improvement after treatment with insulin makes this very unlikely.

Another common differential diagnosis is spinal cord tumour or metastatic lesion; these tend to have pain as the predominant feature, which was not seen here. No such lesion was seen on imaging in this case.

Patients with vitamin B12 and folate deficiency could have similar symptoms along with macrocytic anaemia, and motor symptoms are predominant. The neuropathic symptoms are symmetrical, affecting legs more than arms. The classic hallmark of vitamin B12 deficiency is subacute combined degeneration of the cord, which can present with ataxia, progressive weakness, paraesthesia that may progress to spasticity and paraplegia. They may also have insomnia, irritability, cognitive impairment, dementia, impaired vibration and position sense and positive Romberg test. The imaging, lack of intrinsic factor antibodies and vitamin B12 and folate level in this patient makes this diagnosis unlikely.4

Alcoholic polyneuropathy is a gradual and progressive disease affecting sensory, motor and autonomic nerves and symptoms are symmetrical and distal. The most common neurologic signs are loss of tendon reflexes, defective perception of touch and vibration sensation. This patient had grossly unremarkable reflexes and intact dorsal column along with MCV and GGT within normal range.

Toxic neuropathy is another possible differential, which could be due to drugs, chemical abuse or industrial chemical exposure. The common toxins responsible include lead, mercury, ethylene oxide, carbon disulphide, thallium and dimethylaminopropionitrile. This patient did not have any history of exposure to the above toxins.

Paraneoplastic syndrome and vasculitis may also present with sensory motor symptoms. The imaging and autoimmune screen is against this diagnosis as these did not suggest the presence of suspicious lesions.4

Treatment

This patient was initially commenced on oral antidiabetic medications by his GP and was referred to diabetes specialist nurses who added to alogliptin and empaglaflozin to his existing metformin and gliclazide. The patient, however, continued to lose weight and developed night sweats, tingling in his lower limbs and weakness in his lower limbs due to muscle wasting (figures 5–7) and was referred to ambulatory care by his GP. Patient was seen by medical team and he had urgent CT TAP and CT lumbosacral spine to rule out malignancy. MRI spine was contraindicated in this patient due to his previous gunshot wounds as he had plates inserted in his legs. His blood results are shown in table 1 and CT TAP showed mild diverticulosis and marked paucity of the intra-abdominal fat, with no sinister findings. CT lumbosacral spine showed bilateral L5 spondylolysis with L5-S1 spondylotic changes only. His coeliac and autoimmune screen was negative and anti-insulin antibodies were 7.8 pmol/L (not significant). NCS and electromyography showed sensory action potentials to be either nondetectable or low amplitude while motor responses were slightly slow. Motor conduction test was performed in six nerves and findings were unremarkable in only one nerve. The sensory conduction test was performed on eight nerves and the results were normal in only one nerve. The needle EMG examination was normal in 4 of 11 muscles tested.

Despite excess alcohol consumption the patient’s liver function tests were normal and his CT scan did not show any evidence of chronic liver disease. Patients with DNC need good glycaemic control and require insulin as oral therapies are not sufficient to achieve this. Besides weight loss, autonomic dysfunction, impotence, bowel and bladder problems are quite common in these patients and these usually improve with good glycaemic control.

Outcome and follow-up

The patient was followed up by diabetes team and neurology in the outpatient clinic after 3 months and had good glycaemic response to insulin therapy. He had gained 10 kg of weight and has remarkable improvement in his symptoms since commencement of insulin (figures 8–10). He was seen in ambulatory care a further month later and his HbA1c was 50 mmol/mol and other bloods were unremarkable (table 3). He has ongoing follow-up with diabetes and neurology teams.