scholarly journals Extreme Insulin Resistance From Insulin Antibodies (Not Insulin Receptor Antibodies) Successfully Treated With Combination Immunosuppressive Therapy

Diabetes Care ◽  
2016 ◽  
Vol 40 (2) ◽  
pp. e19-e20 ◽  
Author(s):  
Jennifer B. Hao ◽  
Shahnawaz Imam ◽  
Pervaiz Dar ◽  
Maria Alfonso-Jaume ◽  
Noha Elnagar ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Mathilde Sollier ◽  
Marine Halbron ◽  
Jean Donadieu ◽  
Ahmed Idbaih ◽  
Fleur Cohen Aubart ◽  
...  

Background. Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm characterized by an infiltration of organs by Langerin + (CD207+) and CD1a+ histiocytes. Diabetes insipidus is a frequent manifestation of the disease, while diabetes mellitus is very rare. We report the first case of a 20-year-old man suffering from hypothalamopituitary histiocytosis and diabetes mellitus with serum anti-insulin receptor antibodies. Case Presentation. A 20-year-old patient was admitted for the evaluation of growth delay and hyperphagia. HbA1c level and fasting blood glucose were in the normal range. The diagnosis of hypothalamopituitary histiocytosis was based on histological features after biopsy of a large suprachiasmatic lesion identified on magnetic resonance imaging (MRI). Association of vinblastine and purinethol was started followed by a second-line therapy by cladribine. During the follow-up, the patient was admitted for recurrence of hyperglycemic states and extreme insulin resistance. The screening for serum anti-insulin receptor antibodies was positive. Each episode of hyperglycemia appeared to be correlated with tumoral activity and increase in serum anti-insulin receptor antibodies and appeared to be improved when the disease was controlled by chemotherapy. Conclusion. We report the first description of a hypothalamopituitary histiocytosis associated with serum anti-insulin receptor antibodies, extreme insulin resistance, and diabetes. Parallel evolution of glucose levels and serum anti-insulin receptor antibodies seemed to be the consequence of immune suppressive properties of cladribine.


1992 ◽  
Vol 126 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Salvatore Di Paolo

The effect of metformin on insulin binding and insulin action in the presence of anti-insulin receptor antibodies was investigated in a case of type B extreme insulin resistance. Oral administration of metformin (1 500 mg/d) for 10 days significantly decreased plasma blood glucose and insulin levels and enhanced the hypoglycemic response to exogenous insulin. In vitro preincubation of normal erythrocytes with insulin receptor antibody from the patient plus 4× 10−5 mol/l metformin markedly enhanced insulin binding to receptors, compared to cells incubated with antibody alone. This effect was apparent after 2 h, was maximal after 4 h and did not change up to 24 h. Closely similar results were found when human adipocytes were studied. Analysis of binding data confirmed the increase in both receptor number and affinity. One hour exposure of control adipocytes to metformin enhanced basal lipogenesis by more than 30%. Acute exposure of fat cells to the patient's receptor antibodies resulted in a stimulation of glucose transport and a state of severe insulin resistance. The addition of metformin to antibody in preincubation buffer strongly enhanced basal glucose incorporation into lipids, but did not prevent insulin unresponsiveness. It is suggested that metformin increases, possibly through a change in the spatial conformation of insulin receptor within the plasma membrane, the availability of preexisting receptors to insulin binding and/or decreases the availability of specific epitopes to antibody anchoring. Further, in the model of insulin resistance described here, metformin enhanced the basal rate of glucose transport through a direct insulin-mimicking activity and/or a potentiation of the sensitivity of glucose transport to the antibody.


2017 ◽  
Vol 1 (12) ◽  
pp. 1435-1439 ◽  
Author(s):  
Lavanya Viswanathan ◽  
Imali Sirisena

Abstract Type B insulin resistance is a rare syndrome characterized by fluctuating glucose levels (ranging from hyperglycemia with extreme insulin resistance to intractable hypoglycemia without exogenous insulin administration), high serum insulin levels, and insulin receptor autoantibodies. Most cases occur in the African American population in association with other underlying autoimmune systemic diseases. Treatments with high-dose steroids, immunosuppressants, and plasmapheresis have been used, with variable outcomes, in patients without spontaneous remission. We report the case of a 60-year-old African American woman with history of systemic lupus erythematosus presenting with extreme fluctuations in glucose levels, ranging from severe hyperglycemia to refractory hypoglycemia, with high serum concentration of insulin in both phases. Her presentation and phenotype were very similar to those seen in known cases of type B insulin resistance associated with insulin receptor antibodies. Treatment in other reported cases used a combination of high-dose steroids and immunosuppressants. We tried high-dose steroids, azathioprine, and intravenous immunoglobulins, which resulted in improvement and barely detectable insulin receptor antibody. We present a case of type B insulin resistance with abnormally low titers of insulin receptor antibodies despite a typical clinical course and response. Future research is needed to improve diagnosis and treatment in this rare disease.


Science ◽  
1988 ◽  
Vol 240 (4853) ◽  
pp. 787-790 ◽  
Author(s):  
T Kadowaki ◽  
C. Bevins ◽  
A Cama ◽  
K Ojamaa ◽  
B Marcus-Samuels ◽  
...  

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