LETTERS AND COMMENTS years earlier. The boy in the 3rd case has susceptibility genes and autoantibodies but still has normal (B-cell function. If he remains antibody positive, he may very well develop diabetes. Thus, all 3 cases support the usefulness of immunogenetic markers of prediabetes. The fact that the third patient developed psychiatric difficulties is probably a coincidence. In my experience (—2000 children tested and >12 found positive) and in the even greater experience of other investigators ( 2 - 6), to my knowledge, no such case has been found. In fact, a positive attitude of the tested families has been reported (7). Conclusions drawn from one case vis-a-vis such a large number of cases are misleading. Bell et al. also express their concern about cyclo- sporin treatment in diabetic children. This concern is shared by many, including myself. Cyclosporin should only be used in carefully planned and conducted ran- domized trials. In fact, I question why patient 1 was treated with cyclosporin in what seems a rather casual context. However, cyclosporin is not the only type of treatment being studied for diabetes. There are other intervention protocols (e.g., nicotinimide) that seem to be generally free of toxicity and offer some promise of inducing remissions. These drugs are already being tested in prediabetic individuals. Even if no intervention means were available, study of the autoimmune dysfunction in the prehyperglycemic stage of type I diabetes would still be of great interest to further characterize the autoimmune pathogenesis of this disorder. If Bell et al. meant that none of these ac- tivities are ready to be adopted by general practitioners, then I would wholeheartedly agree. However, the mes- sage I perceived was one of condemnation of these stud- ies, which I think is inappropriate. JOSE BARBOSA, MD insulin-dependent diabetes mellitus. JAMA 254:1469-72, 1985 Riley W, Krischer J, Clarke D, Malone J, Rotter J, Shah S, Vadheim C: Islet cell antibodies (ICA): relative risk (RR) of developing insulin dependent diabetes (IDD) is 166 (Ab- stract)! Diabetes 36:70A, 1987 Johnson SB, Hansen CA, Nurick M: Will I get diabetes? The psychological impact of ICA screening (Abstract)? Di- abetes 36:72A, 1987 REPLY The intent of our letter to Diabetes Care was to em- phasize the point to which Dr. Barbosa refers, namely that immunogenetic diagnosis of prediabetes has not yet advanced to the point that it is of use to the practitioner. In fact, unless such practices are a part of ongoing stud- ies of the immunologic basis of type I (insulin-depend- ent) diabetes, they may cause undue confusion on the part of the practitioner and his or her patient. We strongly support the ongoing studies that are attempting to un- ravel the autoimmune basis of type I diabetes mellitus and to capitalize on this information to develop rational preventive and therapeutic strategies. DAVID S.H. BELL, MD REX S. CLEMENTS, JR., MD From the Division of Endocrinology and Metabolism, The University of Ala- bama at Birmingham, Birmingham, Alabama. Address correspondence and reprint requests to Rex S. Clements, Jr., MD, Division of Endocrinology and Metabolism, The University of Alabama at Bir- mingham, University Station, Birmingham, AL 35294. From the Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Address correspondence and reprint requests to Jose Barbosa, MD, Depart- ment of Medicine, University of Minnesota, Phillips-Wangensteen Building, 516 Delaware Street, SE, Minneapolis, MN 55455-0311. REFERENCES 1. Bell DSH, Acton RT, Barger BO, Vanichanan C, Clements RS Jr: Futility of predicting onset of type I diabetes mellitus (Letter). Diabetes Care 10:788-89, 1987 2. Srikanta S, Ganda OP, Eisenbarth GS, Soeldner JS: Islet cell antibodies and beta-cell function in monozygotic triplets and twins initially discordant for type I diabetes. N Engl ] Med 308:322-25, 1983 3. Bottazzo GF, Florin-Christensen A, Doniach D: Islet cell antibodies in diabetes mellitus with autoimmune polyen- docrine deficiencies. Lancet 2:1279-83, 1974 4. Keller U, Beglinger CH, Berger W: Identification of sub- jects with a high risk of developing type I (insulin depend- ent) diabetes. Diabetologia 28:57-58, 1985 5. Gingsberg-Fellner F, Witt M, Franklin B, Yagihashi S, To- guchi Y, Dobersen M, Rubinstein P, Notkins A: Triad of markers for identifying children at high risk of developing DNA Polymorphism of the Insulin Gene, Diabetes, and Severe Obesity Some reports have suggested that alleles with larger insertion in the 5'-flanking region of the insulin gene (type 3 allele) may be genetic markers of non-insulin- dependent (type II) diabetes (1-5). Aoyama et al. (5) have recently reported in this journal that frequency of larger 5'-flanking insertion is particularly high in non- overweight and <40 yr-of-age type II diabetic patients. In their study, type 3 allele has been found not related to the excess body fat. In our study, complementary to that by Aoyama, we aimed to evaluate the predictive value of type 3 allele on the worsening to type II diabetes of severely obese patients with previous impaired glu- cose tolerance (IGT). Twenty-six (17 females and 9 males) severely obese DIABETES CARE, VOL. 11, NO. 6, JUNE 1988 511