A 59-year old Iranian man was referred to the emergency department complaining of pain in lower limbs, tingling, weakness, impaired bilateral lower limb movement, foot drop, and frequent urination. He was diagnosed with type 2 DM 18 years before admission due to episodes of polydipsia and polyuria. However, initial treatment with the prescription of glibenclamide (10 mg/day), metformin (2000 mg/day), and dietary changes were unsuccessful, and fasting blood glucose concentration was maintained within the approximate range of 8.5 to 11 mmol/L(153-198 mg/dL).
Two years prior to admission, oral antidiabetic medication was suspended, and treatment with Neutral Protamine Hagedorn (NPH) insulin was initiated at doses of 30 IU in the morning and 20 IU at night, as well as 10 IU of regular insulin before meals. The patient had poor treatment compliance, and insulin doses were progressively increased to 240 IU (total daily dose), as well as the resumption of metformin (2000 mg/day) and liraglutide 2.4 (mg/day). His self-monitoring blood glucose ranges were 300 to 450 mg/dL. The patient was admitted with persistent symptoms, and random glucose measurement was 16.6 mmol/L (300 mg/dL).
Besides the past medical history of type 2 DM, he suffered from diabetic polyneuropathy and ischemic heart disease. His drug history was human insulin 240 IU (total daily dose), liraglutide (2.4 mg/day), metformin (2000 mg/day), aspirin (80 mg/day), valsartan (80 mg/day), bisoprolol (2.5 mg/day), and hydrochlorothiazide (25 mg/day).
On physical examinations, the patient was alert, and his vital signs were stable. The cardiopulmonary examination was unremarkable, but acanthosis nigricans and skin tags were observed in his neck (Figure 1). His body mass index was 30 kg/m2. Neurological examinations showed no deep tendon reflex in lower limbs, disturbed sense of position, paresthesia in socks and gloves distribution, and reduced force in lower limbs (4/5) compared to upper limbs (5/5). His Gowers' sign was also found to be positive.
The patient's insulin dose was increased to 530 IU (total daily dose) during his admission, but he had uncontrolled blood glucose levels (HbA1c of 16.1% and fasting blood sugar (FBS) ranges of 400 to 500 mg/dL). Due to a daily insulin requirement of more than 2 IU/kg, the patient was diagnosed with severe insulin resistance. Other potential causes of high blood sugar, including pharmacological, neoplastic, infectious, and autoimmune etiologies, were ruled out. Blood biochemistry profile showed normal kidney and liver function tests. As the aforementioned tests were negative, TBIRS was considered a potential diagnostic hypothesis, and radioimmunoassay (Synlab, Barcelona, Spain) showed autoantibodies against the insulin receptor with a value of 5.23 U/mL (normal range: less than 1 U/mL).
On the other hand, because of the pain, tingling, and weakness of the lower limbs, the patient underwent Electromyography (EMG) and nerve conduction velocity (NCV) test, which revealed chronic axonal sensory-motor polyneuropathy suggestive of CIDP. Neurology consultation was requested, and 12 sessions of plasmapheresis were initiated (1500 L in every session). During initial sessions of plasmapheresis, his pain, weakness, movement disorders of the lower extremities, and blood glucose levels improved significantly; However, due to the patient's refusal to continue plasmapheresis, oral prednisolone (60 mg/day) was initiated during hospitalization leading to amelioration of his neurological manifestations and significant blood glucose control. By the time of discharge, human insulin was discontinued, and he had controlled blood glucose with oral medications and homologous insulin (lispro). He was then discharged with prednisolone tablets (30 mg/day), homologous insulin (total dose of 100 IU/day), liraglutide (1.8 mg/day), acarbose (150 mg/day), metformin (1500 mg/day), glibenclamide (20 mg/day), and pioglitazone (30 mg/day).
In his follow-up 3 months after discharge, he reported significant improvements in his lower limb symptoms, but he still had mild pain in the proximal parts of his lower limbs. The daily dose of prednisolone was decreased to 15 mg/day. His FBS and HbA1c were also in acceptable ranges (120-150 mg/dL and 7.8%, respectively). Timeline of blood glucose, insulin dosages as well as HbA1c levels are illustrated in Figure 2.