Clopidogrel

Abstract

Insulin autoimmune syndrome following misuse: case report A 66-year-old man developed insulin autoimmune syndrome (IAS) due to misuse of clopidogrel. The man presented to the hospital for investigation and management of episodes of sweating and palpitation for 22 days. Upon anamnesis, he reported that 22 days prior to this presentation, he had started having episodes of paroxysmal palpitations, sweating and hunger sensation without obvious precipitating factors, which were obvious at night and were noted to be improved after eating. At the time of onset of these symptoms, he noted that his blood glucose level fluctuated between 2.2–3.5 mmol/L. At that time, he visited another hospital, where laboratory examination revealed glycosylated haemoglobin (HbAlc) of 5.6%, random plasma glucose was between 2.79–3.52 mmol/L, serum insulin level was between 1089.45–1168.13 pmol/L and C-peptide level was between 10.32–15.45 μg/L. His blood sample showed a positive result for insulin autoantibodies (IAA), and a negative result for anti-pancreatic islet cell antibody (ICA) and glutamate-carbase antibody (GADA). His abdominal magnetic resonance imaging (MRI) examination, antinuclear antibodies test and other laboratory parameter were noted to be normal. Multiple examinations of plasma glucose showed a <2.8 mmol/L level of glucose which confirmed the diagnosis of hypoglycaemia. In that hospital, the man was treated with glucose injection, dexamethasone and octreotide. However, the palpitations and sweating persisted, and he presented to this hospital (The current presentation). He was therefore admitted for management of the hypoglycaemia and due to a high possibility of IAS. Since the onset of the disease, he had clear consciousness, fatigue, poor mental state, unconscious disorder, poor night rest, vomiting, a good diet, normal urination and defecation. Upon further investigation of his ongoing medications, it was revealed that he had been taking oral clopidogrel 150mg along with unspecified metabolites containing thiol group, on his own due to dizziness and fatigue (drug-misuse). He did not have any significant medical history of cerebrovascular and cardiovascular diseases, malignant tumours, diabetes, thyroid diseases, trauma, surgery, drug allergy, exogenous administration of insulin and other special drugs. Upon admission, a laboratory examination was performed which revealed plasma glucose of 2.4 mmol/L, synchronous serum insulin 13758.00 mIU/L (after dilution), C-peptide 11.63 μg/L. After 30 minutes, his plasma glucose was 1.45 mmol/L, insulin was 22024.00 mIU/L and C-peptide level was 16.68 μg/L. The dynamic blood glucose monitoring suggested that the blood glucose fluctuated at 2.20-13.90 mmol/L, and hypoglycemia mostly occurred at night, at the fasted state and before meals, and hyperglycemia after meals was rare. His IAA level was >50.00 IU/mL (normal reference value 0.00–0.40 IU/mL). Human leukocyte antigen typing was DRB1*0403 and 0701, DQB1* 0302 and 0202. His electrocardiogram examination, upper abdominal ultrasound and other laboratory test were noted to be normal. Based on the laboratory test results and medical history, he was diagnosed with IAS. Since, the symptoms of hypoglycaemia started occurring after initiation of clopidogrel, it was concluded that the IAS was possibly induced by misuse of clopidogrel. Clopidogrel was therefore discontinued. His dietary structure was also adjusted with low carbohydrates, high fat and high protein drinks, and meals were added once every 3 hours. Additionally, acarbose therapy was initiated. Following these corrective measures, his blood glucose remained stable. Then, he was discharged from the hospital in a stable condition. Five months after discharge, the serum insulin and C-peptide levels decreased significantly and the IAA turned negative. Thereafter, acarbose was discontinued, and the frequency of meals was also reduced, and paroxysmal sweating and palpitations did not occur thereafter.