Endocrine Abstracts

Introduction: Insulin autoimmune syndrome (IAS) is a clinical condition characterized by the presence of autoantibodies to insulin or insulin receptors in patients not previously treated with insulin. This syndrome has been reported mainly in Asia, and it is a rare cause of hypoglycemia in Caucasians. So far there are no reports of IAS in patients with type 2 diabetes mellitus never treated with insulin.

Case report: The authors describe a 59-year-old Caucasian male, diagnosed type 2 diabetes 5 years previously, treated with metformin and gliclazide, referred for hypoglycemic episodes in fasting and late postprandial period. Initial laboratory evaluation revealed fasting glucose=123 mg/dl, HbA1c=7.1%, fasting insulin=1173.3 uUI/ml (normal range: 5–20 uUI/ml), fasting proinsulin=89.6 pmol/l (normal range: <9.4 pmol/l), C-peptide=8.64 ng/ml (normal range: 0.9–7.1 ng/ml), anti-insulin antibodies=201.1 U/ml (positive if >0.5), antinuclear antibodies>1/160, and negativity for anti-IA2, anti-GAD and anti-ICA antibodies. Further serologic and hormonal examination was unremarkable. During a 72 h fasting test, the patient had glucose levels between 51 mg/dl (at 6 h fast) and 153 mg/dl associated with insulin levels of 2496 uUI/ml at the beginning and 705 uUI/ml at the end of the test. Imaging study using angio-CT-scan did not show any morphological pancreatic abnormality. HLA class II typing revealed the presence of DRB1*04, DRB1*03 e DQB1* alleles. After one year of follow-up, our patient, treated with metformin, has less frequent symptomatic hypoglycemia. Nevertheless, continuous glucose monitoring for 72 h, revealed repeated fasting hypoglycemia, with minimum level of 40 mg/dl, and postprandial hyperglycemia. Recent laboratory examination showed fasting insulin=233.8 uUI/ml, C-peptide=4.44 ng/ml, HbA1c=7.9% and anti-insulin antibodies=157.2 U/ml.

Conclusion: This is a rare case of IAS in a patient with type 2 diabetes mellitus not previously exposed to insulin. The development of these antibodies may be related to a genetic susceptibility, since HLA-DRB1*04 has been reported in strong association with this syndrome.