Insulin-like Growth Factor 1 Therapy for Type B Insulin Resistance

1 August 1997 | Volume 127 Issue 3 | Pages 245-246

TO THE EDITOR:

The type B insulin-resistance syndrome is characterized by the presence of anti-insulin receptor antibodies that cause severe insulin resistance [1, 2]. A 44-year-old, nonobese woman with Hashimoto thyroiditis and the Sjogren syndrome demonstrated severe insulin resistance and acanthosis nigricans. Plasma glucose and insulin levels during oral glucose tolerance testing were 7.3 to 22.1 mmol/L and 4264 to 10 986 pmol/L, respectively. Anti-insulin receptor antibodies were detected in serum, but results of tests for anti-insulin antibody were negative. When oral prednisolone was administered at a starting dose of 40 mg, severe hyperglycemia immediately developed. Because massive insulin injections had no appreciable effect on hyperglycemia even while the patient was receiving 5 mg of prednisolone, we attempted human recombinant insulin-like growth factor 1 (IGF-1) injection (Fujisawa Pharmaceutical, Osaka, Japan). The high glucose levels were not altered on days 1 and 2 but declined rapidly thereafter. When IGF-1 treatment was discontinued on day 6, glucose levels again increased (Figure 1). The severe hyperglycemia finally disappeared after cessation of steroid treatment.

View larger version (18K): [in this window] [in a new window]   Figure 1. Changes in plasma glucose levels during administration of oral prednisolone and subcutaneous injections of human recombinant insulin-like growth factor 1 (IFG-1) (20 mg).

 

Glucocorticoids produce insulin resistance by creating a postreceptor defect [3]. Therefore, if anti-insulin receptor antibodies are not effectively reduced by steroid treatment, insulin resistance will be increased by the addition of a postreceptor defect. As it has in patients with other severe insulin-resistance syndromes [4], IGF-1 injection successfully ameliorated hyperglycemia in a type B patient. However, if a type B patient has antibodies to IGF-1 receptors as well as insulin receptors, IGF-1 injection cannot exert hypoglycemic effects. Indeed, a high incidence of anti-IGF-1 receptor antibodies has been reported in type B patients [5]. Fortunately, our patient did not have these antibodies and IGF-1 therapy was therefore effective. For the treatment of steroid-resistant type B patients, IGF-1 may prove useful.

Author and Article Information

Top Author & Article Info References

Showa University School of Medicine; Tokyo 142, Japan

References

Top Author & Article Info References

1. Kahn CR, Flier JS, Bar RS, Archer JA, Gorden P, Martin MM, et al. The syndromes of insulin resistance and acanthosis nigricans. N Engl J Med. 1976; 294:739-45.

2. Tsokos GC, Gorden P, Antonovych T, Wilson CB, Balow JE. Lupus nephritis and other autoimmune features in patients with diabetes mellitus due to autoantibody to insulin receptors. Ann Intern Med. 1985; 102:176-81.

3. Weinstein SP, Paquin T, Pritsker A, Harber R. Glucocorticoid-induced insulin resistance: dexamethasone inhibits the activation of glucose transport in rat skeletal muscle by both insulin- and non-insulin-related stimuli. Diabetes. 1995; 44:441-5.

4. Kuzuya H, Matusuura N, Sakamoto M, Makino H, Sakamoto Y, Kadowaki T, et al. Trial of insulin-like growth factor 1 therapy for patients with extreme insulin resistance syndromes. Diabetes. 1993; 42:696-705.

5. Tappy L, Fujita-Yamaguchi Y, Lebon TR, Boden G. Antibodies to insulin-like growth factor 1 receptors in diabetes and other disorders. Diabetes. 1988; 37:1708-1914.

About Letters

The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:

•Include no more than 300 words of text, three authors, and five references

•Type with double-spacing

•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.

Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.

Annals welcomes electronically submitted letters.