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Type I Diabetes Mellitus in Monozygotic Twins: Chronic Progressive Beta Cell Dysfunction

S. SRIKANTA, M.D.; O. P. GANDA, M.D.; R. A. JACKSON, M.D.; R. E. GLEASON, Ph.D.; A. KALDANY, M.D.; M. R. GAROVOY, M.D.; E. L. MILFORD, M.D.; C. B. CARPENTER, M.D.; J. S. SOELDNER, M.D.; and G. S. EISENBARTH, M.D., Ph.D.
[+] Article and Author Information

Grant support: in part by grant AM-09481 and AM-25778-04 from the National Institutes of Health, a grant from the Kroc Foundation, and a Career Development Award from the Juvenile Diabetes Foundation.

▸Requests for reprints should be addressed to George S. Eisenbarth, M.D., Ph.D.; Joslin Diabetes Center, Research Division, One Joslin Place; Boston, MA 02215.


Boston, Massachusetts


© 1983 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1983;99(3):320-326. doi:10.7326/0003-4819-99-3-320
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In a prospective 21-year study, islet cell antibodies and beta cell function were serially assessed in 24 monozygotic twins initially discordant for type I diabetes mellitus. Eighteen of 21 twins typed had HLA-DR3 or HLA-DR4 antigens. During the follow-up, 4 twins developed type I diabetes mellitus, and in 3 of these 4 twins islet cell antibodies preceded the diagnosis of clinical diabetes mellitus by greater than 8, 5 and 7 years respectively. During the "prediabetic phase," the presence of islet cell antibodies was temporally associated with a progressive decline in first phase insulin response to intravenous glucose. Elevations in fasting blood glucose and abnormalities on oral glucose tolerance tests appeared only later during the course of the disease. Of the remaining 20 twins who continue to be discordant for type I diabetes mellitus, two have had islet cell antibodies for greater than 1.5 and 1 year respectively. One of these islet cell antibody-positive non-diabetic twins was restudied; despite a fasting blood glucose level of 64 mg/dL, she had a total absence of first phase insulin response to intravenous glucose. There was no evidence of transient islet cell antibody positivity in any of the twins studied. Type I diabetes mellitus in monozygotic twins has a prolonged prediabetic phase of progessive beta cell dysfunction with associated immunologic abnormalities.

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