Management of Insulin Autoimmune Hypoglycaemia: Single‐centre experience from Western India with systematic review of world literature

Abstract

Background: Awareness about Insulin Autoimmune Hypoglycaemia (IAH) and its management remains limited. Methodology:We describe two cohorts: Cohort 1 (n = 7) included patients with IAH from a tertiary care centre in India and Cohort 2 (n = 294) included systematic review of published English literature from PubMed. They were compared with our insulinoma patients (n = 41). Results: Cohort 1 included seven female patients where two had drugs (carbimazole and thiocolchicoside) as triggering factors. Except for one patient requiring oral prednisolone, others had spontaneous remission. The unique features from our series are being first case series of IAH from India and reporting of second case of thiocolchicoside triggered IAH.Cohort 2 had 294 patients identified from 149 publications. Mean age was 54 ± 19 years. Thirty-five different triggers were identified from 160 cases.Antithyroid drugs were most common triggers in Japanese patients and most common HLA allele was DRB1*0406, while it was alpha-lipoic acid and HLA DRB1*0403 in non-Asians. Serum Insulin >100 µIU/mL and insulin to C-peptide molar ratio (ICMR) >0.25 had specificity of 100% and 97.5%, respectively, for IAH as compared to insulinoma. 56% patients had remission with complex carbohydrate diet and trigger removal while 43% required immunosuppressants. 70% achieved remission within 6 months. Conclusions:Middle age remains most common age group. Sulfhydryl drugs are most common triggers. Serum Insulin >100 µIU/mL and ICMR > 0.25 in critical sample are good predictors for diagnosis of IAH, which needs to be confirmed by IAA.Conservative management with dietary modification and trigger removal usually suffices in majority. Rests need immunosuppressants. K E Y W O R D Scase series of IAH, insulin auto-antibodies, insulin autoimmune hypoglycaemia, insulin autoimmune syndrome, management of IAH, systematic review of IAH

Steroid-Refractory Insulin Autoimmune Syndrome Treated With Rituximab and Continuous Glucose Monitoring

“…Our patient was still hypoglycemic despite one month of steroid therapy and was developing signs of steroid toxicity. The treatment options for steroid-refractory IAS are azathioprine, rituximab, and plasmapheresis [2][3][4]. Rituximab was tried in IAS based on the results of the trialNET study, which was conducted for type 1 diabetes patients.…”

“…IAS is a rare autoimmune syndrome first described by Hirata et al in 1970 [ 1 ]. It is characterized by severe attacks of spontaneous hyperinsulinemic hypoglycemia associated with elevated serum immunoreactive insulin levels, increased insulin autoantibody titers, no prior exposure to exogenous insulin, and normal pancreatic beta cells [ 2 , 3 ]. Insulin autoantibodies are usually of immunoglobulin G (IgG) class and polyclonal but can be monoclonal and of IgA or IgM class as well.…”

“…Insulin autoimmune syndrome (IAS) was first described by Hirata in Japan in 1970 [ 1 ], and it is a rare disorder. Only 389 cases of IAS had been reported till 2009, mainly from Japan and China but very few in Caucasians and less than 10 from India [ 2 , 3 ]. IAS is characterized by severe spontaneous attacks of hyperinsulinemic hypoglycemia, high total immunoreactive insulin levels, elevated insulin autoantibody (IAA) titers, no prior exposure to exogenous insulin, and no pathological abnormalities of the pancreatic islet cells [ 4 , 5 ].…”

Scientific opinion on the relationship between intake of alpha‐lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome

“…The presence of the Human Leukocyte Antigen HLA‐DR4 (Uchigata et al., 2010), and in particular the alleles DRB1*04:06 (most of the Asian cases), DRB1*04:03 (most of the Caucasian cases) and DRB1*04:07 (Patel et al., 2020) and to a lesser extent DRB1*04:15 (Cappellani et al., 2018; Cambria et al., 2020) are associated with an increased risk of developing the disease.…”

Insulin Autoimmune Syndrome – A Case Series

“…1 In India, which has a population of more than 1 billion, only 28 cases of IAS have been reported to date, to the best of our knowledge. [2][3][4][5][6][7][8][9][10] IAS is characterised by hyperinsulinaemic hypoglycaemia -elevated insulin autoantibody titres with no prior exposure to exogenous insulin. Most cases of IAS are self-limiting.…”