TO THE EDITOR:
The recent National Institutes of Health (NIH) conference [1] clearly and elegantly outlines the current understanding of the therapeutic use of IGF-I on growth deficits and diabetes.
I was surprised, however, by the negative views on the potential use of IGF-I as an alternative to insulin in patients with extreme insulin resistance. Dr. Skarulis extensively discussed two abstracts: 1) a study of five patients in whom IGF-I did not increase the glucose infusion required to maintain euglycemic levels during an IGF-I infusion and 2) IGF-I treatment in a patient with the Rabson-Mendenhall syndrome who did not achieve glycemic control. However, three peer-reviewed articles show a dramatic effect of short-term (hours) or long-term (months) IGF-I treatment, which achieved improved glycemic control in patients with extreme insulin resistance [2-4]. In addition, Usala and colleagues [4] reported reversal of life-threatening, insulin-resistant diabetes ketoacidosis with IGF-I treatment.
I agree with Dr. Skarulis that the dose, the route of administration, and especially the circulating levels of IGF-binding proteins could explain the differences between her interesting data and the previous published reports. Further studies evaluating the role of the specific receptor responsible for IGF-I hypoglycemic action[5] and the long-term secondary effects of IGF-I treatment in these patients are necessary. Although not all patients with insulin resistance seem to benefit from IGF-I treatment, it should be noted that IGF-I therapy may play an important role in treating patients with severe insulin resistance.
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. Quin JD, Fisher BM, Paterson KR, Inoue A, Beastall GH, MacCuish AC. Acute response to recombinant insulin-like growth factor in a patient with Mendenhall's syndrome [Letter]. N Engl J Med. 1990; 323:1425-6.
3. Kuzuya H, Matsuura N, Sakamoto M, Makino H, Sakamoto Y, Kadowaki T, et al. Trial of insulin-like growth factor I therapy for patients with extreme insulin-resistance syndromes. Diabetes. 1993; 42:696-705.
4. 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.
5. Burguera B, Elton CW, Tapscott EB, Pories WJ, DiMarchi R, Sakano KI, et al. Stimulation of glucose uptake by insulin-like growth factor II in human muscle is not mediated by the insulin-like growth factor II/mannose 6-phosphate receptor. Biochem J. 1994; 300:781-5.
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