title: Life-table analysis of progression to diabetes of anti-insulin autoantibody-positive relatives of individuals with type I diabetes.
abstract: Cytoplasmic islet cell antibody-negative (ICA-; less than 20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulin-dependent) diabetic individuals were studied for competitive insulin autoantibodies (CIAAs) with a radioassay. Overall, 3.7% of first-degree relatives (64 of 1712) were CIAA+. Of ICA- relatives, 2.7% (45 of 1670) exceeded the upper limit of our normal CIAA range (greater than 39 nU/ml), and 45% (19 of 42) of ICA+ relatives exceeded this normal range. Follow-up serums for repeat CIAA determination have been obtained from 16 of the nondiabetic CIAA+/ICA- individuals (time between samples, 0.4-5.8 yr). Fourteen of these 16 (87%) CIAA+/ICA- relatives were found to still be positive on follow-up, and 2 of the relatives who were positive on the first determination were negative on their follow-up test. With a mean follow-up of approximately 2 yr, 4 of 45 (9%) of the CIAA+/ICA- relatives, 5 of 23 (22%) of the ICA+/CIAA- relatives, and 12 of 19 (63%) of the CIAA+/ICA+ relatives developed diabetes. Life-table analysis indicated that, overall, 53% of CIAA+ relatives become diabetic after 5 yr of follow-up versus 65% of ICA+ relatives. Also by life-table analysis, the predicted risk after 5 yr of follow-up for progression to diabetes is 17% for CIAA+/ICA- relatives, 42% for ICA+/CIAA- relatives, and 77% for CIAA+/ICA+ relatives. The highest rate of progression to diabetes was found in ICA+ relatives with CIAA levels greater than 150 nU/ml (100% projected to be diabetic within 5 yr, P less than .008 vs. ICA+/CIAA- relatives).
authors.affiliation: Joslin Diabetes Center, Brigham and Women's Hospital, Boston, MA 02215.
authors.forename: A G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: R
authors.initials: R
authors.lastname: Ziegler
authors.forename: P
authors.initials: P
authors.lastname: Vardi
authors.forename: R A
authors.initials: RA
authors.lastname: Jackson
authors.forename: J S
authors.initials: JS
authors.lastname: Soeldner
authors.forename: G S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D001323:Autoantibodies / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D005190:Family; D005500:Follow-Up Studies; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D015993:Life Tables; D012016:Reference Values; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; C024211:islet cell antibody