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Åke Lernmark

Principal investigator

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Severe insulin resistance in a patient with type 1 diabetes and stiff- man syndrome treated with insulin lispro


  • Irl B. Hirsch
  • David D'Alessio
  • Lily Eng
  • Connie Davis
  • Åke Lernmark
  • Alan Chait

Summary, in English

We describe a patient with type 1 diabetes with recurrent diabetic ketoacidosis and severe insulin resistance. Extensive evaluation of the etiology of the insulin resistance did not reveal an etiology, and well over 1000 U of daily insulin did not prevent the ketoacidosis. Her blood glucose and insulin requirements were improved with glucocorticoids and octreotide, but the effects of both of these agents were short-lived. She was given a trial of insulin lispro with immediate and dramatic effects, lowering her HbA(1c) from 14.6 to 5.1% in 7 months with a decrease in insulin requirements of 1600-100 U per day. Besides her diabetes, she had a history of pain and stiffness affecting numerous muscle groups, and hospitalization was required for pain control. The diagnosis of stiff-man syndrome (SMS) was confirmed with high titers of glutamic acid decarboxylase 65 antibodies in both serum and cerebral spinal fluid. In summary, we describe the first patient with type 1 diabetes, SMS, and severe insulin resistance. Although the etiology of the insulin resistance is unknown, due to the efficacious response to insulin lispro, hydrocortisone, and perhaps octreotide, we propose an immune-mediated etiology. Although rare, this syndrome needs to be considered as an etiology of insulin resistance.

Publishing year







Diabetes Research and Clinical Practice





Document type

Journal article (comment)




  • Glucocorticoid
  • Insulin lispro
  • Insulin resistance
  • Octreotide
  • Stiff man syndrome




  • ISSN: 0168-8227