Risk for developing type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies.
First-degree relatives of Type 1 (insulin-dependent) diabetic patients are at increased risk for developing clinical diabetes. The presence of islet cell or insulin autoantibodies further identifies relatives at greater risk, but not all immunologic-marker-positive relatives progress to disease. Beta-cell dysfunction, however, seems to be more prevalent than clinical Type 1 diabetes, since stable subclinical pancreatic Beta-cell dysfunction may occur. Antibodies against a Mr 64,000 (64K) islet Beta-cell protein, identified as glutamic acid decarboxylase, have been reported both at and several years prior to the clinical onset of Type 1 diabetes. We measured 64K antibodies in first-degree relatives with varying degrees of Beta-cell dysfunction and risk for subsequent Type 1 diabetes to determine whether 64K antibodies improve the predictive power of islet cell antibodies and/or insulin autoantibodies. In the Seattle Family Study first-degree relatives of Type 1 diabetic patients are followed prospectively using detailed Beta-cell function tests, insulin sensitivity, quantitative evaluation of islet cell antibodies and fluid phase assay insulin autoantibodies. 64K antibodies were measured using dog islets. Relatives were selected, based on Beta-cell function to represent individuals at high (n = 6) and low (n = 30) risk for subsequent Type 1 diabetes. The 30 low-risk individuals followed-up for 78 months, had stable Beta-cell function, and six (20%) were negative for all autoantibodies, ten (33%) were positive for insulin autoantibodies, 16 (53%) were islet cell antibody positive while six (20%) were positive for 64K antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Bärmeier
H
H
Department of Medicine, University of Washington, Seattle.
McCulloch
D K
DK
Neifing
J L
JL
Warnock
G
G
Rajotte
R V
RV
Palmer
J P
JP
Lernmark
A
A
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005190:Family; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007330:Insulin Antibodies / Q000032:analysis*; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D012307:Risk Factors
D001323:Autoantibodies; D015415:Biomarkers; D006680:HLA Antigens; D007330:Insulin Antibodies; C024211:islet cell antibody