Evaluation of high insulin antibody response and related clinical outcomes in patients with T1DM or T2DM treated with LY2963016 and Lantus®

A 66-year male with a history of Central Serous Retinopathy presented with recurrent episodes of hypoglycemia. On evaluation, he was found to have insulin-mediated hypoglycemia with serum insulin of 300uIU/ml, C peptide 27.51ng/ml, when the blood glucose was 46mg/dl. High insulin levels above 100uIU/ml, led to suspicion of Autoimmune hypoglycemia and were confirmed by a high anti-insulin antibody titer of 300U/ml. Imaging was negative for Insulinoma. The patient was started on low dose oral prednisolone under ophthalmological monitoring, but as there was no symptomatic improvement, the dose was increased following which there was a flare-up of CSR. The patient was initiated on plasmapheresis following which his hypoglycemia improved with drop in anti-insulin antibody titers to 29U/ml. The patient was maintained on low dose steroids, which were tapered and stopped over the next six months with complete resolution of hypoglycemia and normalization of anti-insulin antibody titers.

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Differences in Humoral Insulin-Antibody Response Among Inbred Lou/M Rats and Epitope Presentation Differences in ELISA and Radioimmune Titration

Diabetes ◽

10.2337/diab.38.7.868 ◽

1989 ◽

Vol 38 (7) ◽

pp. 868-873 ◽

Cited By ~ 2

Author(s):

E. R. Arquilla ◽

S. Edwards ◽

B. R. McDougall ◽

L. Mosqueda ◽

D. P. Stenger

Keyword(s):

Antibody Response ◽

Insulin Antibody

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The HLA-DRB, -DQB polymorphism and anti-insulin antibody response in Slovenian patients with type 1 diabetes

European Journal of Immunogenetics ◽

10.1046/j.1365-2370.2003.00395.x ◽

2003 ◽

Vol 30 (3) ◽

pp. 223-227 ◽

Cited By ~ 9

Author(s):

T. Battelino ◽

N. Uršič-Bratina ◽

V. Dolžan ◽

M. Stopar-Obreza ◽

P. Pozzilli ◽

...

Keyword(s):

Type 1 Diabetes ◽

Antibody Response ◽

Insulin Antibody

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Hyperlabile diabetes accompanied by insulin resistance.

Clinical Chemistry ◽

10.1093/clinchem/27.8.1463 ◽

1981 ◽

Vol 27 (8) ◽

pp. 1463-1464 ◽

Cited By ~ 4

Author(s):

A Renie ◽

R G Hamilton ◽

N F Adkinson ◽

M S Rendell

Keyword(s):

Insulin Resistance ◽

Solid Phase ◽

Insulin Requirement ◽

Porcine Insulin ◽

Insulin Antibody ◽

Insulin Dosage ◽

Diabetic Patients ◽

Free Insulin ◽

High Insulin ◽

Solid Phase Radioimmunoassay

Abstract It is generally held that high insulin antibody concentrations, by "buffering" abrupt swings in free insulin concentrations after injections of exogenous insulin, tend to stabilize blood glucose variations in diabetic patients. However, we encountered a patient with extremely labile diabetes coexisting with insulin resistance. This patient's injections were switched to pure porcine insulin from his usual mixed bovine/porcine insulin, in an effort to decrease his insulin requirement. This treatment was successful, and, as his insulin dosage decreased, his diabetic lability diminished substantially. His diabetes was eventually considered stabilized on about 22 units of porcine insulin daily. The serial decrease in his insulin antibody concentrations, monitored by use of solid-phase radioimmunoassay, paralleled the disappearance of his diabetic lability as well as the decrease in his insulin requirement.

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Animal insulin therapy induces a biased insulin antibody response that persists for years after introduction of human insulin

Acta Diabetologica ◽

10.1007/s00592-009-0135-2 ◽

2009 ◽

Vol 47 (2) ◽

pp. 131-135 ◽

Cited By ~ 11

Author(s):

Shilpa Oak ◽

Thanh-Hien Thi Phan ◽

Lisa K. Gilliam ◽

Irl B. Hirsch ◽

Christiane S. Hampe

Keyword(s):

Antibody Response ◽

Insulin Therapy ◽

Human Insulin ◽

Insulin Antibody

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A novel approach to a rare case of non-islet cell hypoglycaemia

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-21-0040 ◽

2021 ◽

Vol 2021 ◽

Author(s):

R K Dharmaputra ◽

K L Wan ◽

N Samad ◽

M Herath ◽

J Wong ◽

...

Keyword(s):

Plasma Exchange ◽

Islet Cell ◽

B Lymphocyte ◽

Serum Insulin ◽

Insulin Antibody ◽

Lymphocyte Depletion ◽

Insulin Levels ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome ◽

High Insulin

Summary Insulin autoimmune syndrome (IAS) is a rare cause of non-islet cell hypoglycaemia. Treatment of this condition is complex and typically involves long-term use of glucocorticoids. Immunotherapy may provide an alternative in the management of this autoimmune condition through the suppression of antibodies production by B-lymphocyte depletion. We present a case of a 62-year-old male, with refractory hypoglycaemia initially presenting with hypoglycaemic seizure during an admission for acute psychosis. Biochemical testing revealed hypoglycaemia with an inappropriately elevated insulin and C-peptide level and no evidence of exogenous use of insulin or sulphonylurea. Polyethylene glycol precipitation demonstrated persistently elevated free insulin levels. This was accompanied by markedly elevated anti-insulin antibody (IA) titres. Imaging included CT with contrast, MRI, pancreatic endoscopic ultrasound and Ga 68-DOTATATE position emission tomography (DOTATATE PET) scan did not reveal islet cell aetiology for hyperinsulinaemia. Maintenance of euglycaemia was dependent on oral steroids and dextrose infusion. Complete resolution of hypoglycaemia and dependence on glucose and steroids was only achieved following treatment with plasma exchange and rituximab. Learning points Insulin autoimmune syndrome (IAS) should be considered in patients with recurrent hyperinsulinaemic hypoglycaemia in whom exogenous insulin administration and islet cell pathologies have been excluded. Biochemical techniques play an essential role in establishing high insulin concentration, insulin antibody titres, and eliminating biochemical interference. High insulin antibody concentration can lead to inappropriately elevated serum insulin levels leading to hypoglycaemia. Plasma exchange and B-lymphocyte depletion with rituximab and immunosuppression with high dose glucocorticoids are effective in reducing serum insulin levels and hypoglycaemia in insulin autoimmune syndrome (IAS). Based on our observation, the reduction in serum insulin level may be a better indicator of treatment efficacy compared to anti-insulin antibody (IA) titre as it demonstrated greater correlation to the frequency of hypoglycaemia and to hypoglycaemia resolution.

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