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

Diabetes Res Clin Pract. 1998 Sep;41(3):197-202. doi: 10.1016/s0168-8227(98)00072-2.


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 HbA1c 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Body Mass Index
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetic Ketoacidosis / complications*
  • Diabetic Ketoacidosis / drug therapy
  • Diabetic Ketoacidosis / physiopathology
  • Female
  • Glutamate Decarboxylase / blood
  • Glutamate Decarboxylase / cerebrospinal fluid
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin A / analysis
  • Hormones / therapeutic use
  • Humans
  • Hydrocortisone / therapeutic use
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / analogs & derivatives*
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Insulin Lispro
  • Insulin Resistance / physiology*
  • Octreotide / therapeutic use
  • Prednisone / therapeutic use
  • Stiff-Person Syndrome / complications*
  • Stiff-Person Syndrome / physiopathology


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hormones
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • Glutamate Decarboxylase
  • Octreotide
  • Prednisone
  • Hydrocortisone