Analysis of metabolic progression to type I diabetes in ICA+ relatives of patients with type I diabetes.
We intensively studied 5 islet cell-antibody-positive (ICA+) first-degree relatives of type I (insulin-dependent) diabetic patients before overt diabetes. In total, 55 intravenous glucose tolerance tests (IVGTTs) and 83 fasting plasma glucose determinations were made over a maximum 4-yr period before diabetes. The 5 prediabetic relatives (not diabetic when initially studied but subsequently progressed to overt diabetes) as a group showed a progressive rise in fasting glucose (r = 0.58, P less than 0.001, slope = 23.1 mg.dl-1.yr-1) and glucose at 60 min in IVGTT (r = 0.46, P = 0.01, slope = 47.5 mg.dl-1.yr-1) beginning 1.5 yr before diabetes. During the 4.0- to 1.5-yr period before overt diabetes, no change was observed in fasting glucose or glucose at 60 min on IVGTT (fasting glucose: r = 0.21, P = 0.18, slope = 2.1 mg.dl-1.yr-1; 60-min glucose: r = 0.08, P = 0.72, slope = 2.9 mg.dl-1.yr-1). The positive predictive value for a fasting glucose greater than 108 mg/dl to be within 1.5 yr of diabetes was 100% (11 of 11 values). The negative predictive value of a stimulated insulin (1-min + 3-min insulin - 2 X basal insulin) level greater than 24 microU/ml to be greater than 1.5 yr from diabetes was 90% (9 of 10 values) and 100% (10 of 10 values) at greater than 1 yr from overt diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
Bleich
D
D
Joslin Diabetes Center, Brigham and Women's Hospital, Boston, Massachusetts.
Jackson
R A
RA
Soeldner
J S
JS
Eisenbarth
G S
GS
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis*; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D004200:Diseases in Twins; D005190:Family; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D011236:Prediabetic State / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D013997:Time Factors; D014430:Twins, Monozygotic
D001323:Autoantibodies; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; C024211:islet cell antibody