Relationship between first-phase insulin secretion and age, HLA, islet cell antibody status, and development of type I diabetes in 220 juvenile first-degree relatives of diabetic patients.
OBJECTIVE
To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes.


METHODS
Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3-29 yr) of diabetic patients; 75 underwent two or more tests.


RESULTS
At the first test, insulin responses correlated with age in ICA- children less than or equal to 11 yr old (r = 0.46, p less than 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children less than 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA- subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA- subjects displayed distinct changes; the mean +/- SE insulin response increased in ICA- subjects from 619.2 +/- 40.8 to 716.4 +/- 50.4 pM (P less than 0.001) but declined in ICA+ subjects from 403.2 +/- 91.8 to 313.8 +/- 67.2 pM (P less than 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA- subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response.


CONCLUSIONS
Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.
Robert
J J
JJ
Pediatric Endocrinology and Diabetes Unit, Hospital for Sick Children, Paris, France.
Deschamps
I
I
Chevenne
D
D
Roger
M
M
Mogenet
A
A
Boitard
C
C
D000367:Age Factors; D001323:Autoantibodies / Q000032:analysis*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D005190:Family; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006680:HLA Antigens / Q000032:analysis*; D006650:Histocompatibility Testing; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male
D001323:Autoantibodies; D006442:Glycated Hemoglobin; D006680:HLA Antigens; D007328:Insulin; C024211:islet cell antibody