LETTER
Risks and Benefits of Insulin-like Growth Factor
Anton-Lewis Usala, MD
1 October 1994 | Volume 121 Issue 7 | Pages 549-550
TO THE EDITOR:
I report some additional uses and potentially serious side effects of intravenous IGF-I not mentioned in the recently published NIH conference on clinical uses of IGF-I [1]. We have shown that high-dose (500 µg/kg of body weight), bolus intravenous IGF-I therapy resulted in both temporal and prolonged insulin sensitivity in two patients with type I diabetes complicated by severe insulin resistance [2-4]. In both patients, daily subcutaneous IGF-I administration with insulin resulted in temporal glycemic control, but severe resistance returned 48 hours after therapy was discontinued. Therapy had to be discontinued after 2 to 6 weeks because of severe arthralgia and multiple cranial nerve palsies.
However, 500-µg/kg IGF-I bolus therapy (with maximal serum IGF-I concentrations of approximately 6000 µg/L) resulted in daily insulin dose requirement reductions from several thousand units administered intravenously to 1 U/kg daily given subcutaneously for 7 to 10 days. Lower serum IGF-I concentrations resulting from 250-µg/kg boluses were ineffective in decreasing serum glucose acutely or in inducing sustained insulin sensitivity [4].
Most importantly, both patients experienced severe dyspnea associated with a short-term decrease in serum phosphate levels within 10 minutes of receiving the intravenous IGF-I bolus [2, 3]. This side effect was reversed and prevented during subsequent IGF-I administration by coadministration of intravenous potassium phosphate. When an adequate phosphate dose was administered, weekly or alternate-week bolus IGF-I therapy had no discernible adverse reactions in the two patients.
1. Bondy CA, Underwood LE, Clemmons DR, Guler HP, Bach MA, Skarulis M. Clinical uses of insulin-like growth factor I. Ann Intern Med. 1994; 120:593-601.
2. Usala AL, Madigan T, Burguera B, Sinha MK, Caro JF, Cunningham P, et al. Brief report: Treatment of insulin-resistant ketoacidosis with insulin-like growth factor I in an adolescent with insulin diabetes. N Engl J Med. 1992; 327:853-7.
3. Usala AL, Powell JP, Madigan T, Burguera B, Usala SJ. Intravenous or subcutaneous IGF-I therapy induces symptomatic hypophosphatemia in patients with severe insulin resistance [Abstract]. 76th Annual Endocrine Society Meeting; 1993:131.
4. Usala AL, Madigan T, Burguera B, Sinha MK, Cefalu W, Powell JP, et al. High dose intravenous, but not low dose subcutaneous, IGF-I induces sustained insulin sensitization in severely resistant type I diabetes. J Clin Endocrinol Metab. 1994; [In press].
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