Prognostic performance of metabolic indexes in predicting onset of type 1 diabetes.
OBJECTIVE
In this investigation we evaluated nine metabolic indexes from intravenous glucose tolerance tests (IVGTTs) and oral glucose tolerance tests (OGTTs) in an effort to determine their prognostic performance in predicting the development of type 1 diabetes in those with moderate risk, as defined by familial relation to a type 1 diabetic individual, a positive test for islet cell antibodies and insulin autoantibody, but normal glucose tolerance.


METHODS
Subjects (n = 186) who had a projected risk of 25-50% for developing type 1 diabetes within 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial-Type 1. Prognostic performance of the metabolic indexes was determined using receiver operating characteristic (ROC) curve and survival analyses.


RESULTS
Two-hour glucose from an OGTT most accurately predicted progression to disease compared with all other metabolic indicators with an area under the ROC curve of 0.67 (95% CI 0.59-0.76), closely followed by the ratio of first-phase insulin response (FPIR) to homeostasis model assessment of insulin resistance (HOMA-IR) with an area under the curve value of 0.66. The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values >0.60. The hazard ratio for those with 2-h glucose ≥ 114 mg/dl compared with those with 2-h glucose <114 mg/dl was 2.96 (1.67-5.22).


CONCLUSIONS
The ratio of FPIR to HOMA-IR from an IVGTT provided accuracy in predicting the development of type 1 diabetes similar to that of 2-h glucose from an OGTT, which, because of its lower cost, is preferred. The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.
Xu
Ping
P
Department of Pediatrics, College of Medicine, University of South Florida, Tampa, Florida, USA. xup@epi.usf.edu
Wu
Yougui
Y
Zhu
Yiliang
Y
Dagne
Getachew
G
Johnson
Giffe
G
Cuthbertson
David
D
Krischer
Jeffrey P
JP
Sosenko
Jay M
JM
Skyler
Jay S
JS
D000293:Adolescent; D017668:Age of Onset; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
D001786:Blood Glucose
Diabetes Care. 2007 Sep;30(9):2314-20
17536068
Mayo Clin Proc. 2000 Feb;75(2):165-72
10683656
Diabetes Care. 2008 Mar;31(3):528-33
18000175
Diabetes Care. 2007 Jan;30(1):38-42
17192330
J Clin Endocrinol Metab. 2003 Jan;88(1):103-8
12519837
Diabetes. 2010 Mar;59(3):679-85
20028949
Radiology. 1982 Apr;143(1):29-36
7063747
Mayo Clin Proc. 2000 Mar;75(3):255-64
10725952
J Clin Invest. 1994 Jun;93(6):2403-7
8200974
Pediatr Diabetes. 2001 Jun;2(2):71-82
15016201
Diabetes Care. 2006 Mar;29(3):643-9
16505520
J Pediatr. 2001 Feb;138(2):244-9
11174623
Diabetes. 1999 Jan;48(1):170-5
9892239
Diabetes. 2004 Jan;53(1):250-64
14693724
Diabetes Care. 1997 Jul;20(7):1183-97
9203460
Diabetes Care. 2008 Nov;31(11):2188-92
18650369
Diabetes. 1996 Nov;45(11):1631-4
8866571
Diabetes Metab Res Rev. 2002 May-Jun;18(3):192-200
12112937
Adv Exp Med Biol. 2004;552:268-90
15622968
Diabetes Care. 2007 Jun;30(6):1544-8
17384342
Diabetes Care. 2006 Mar;29(3):662-7
16505523
N Engl J Med. 1990 Oct 25;323(17):1167-72
2215594
Diabetologia. 2000 Jan;43(1):61-8
10663217
Biometrics. 1988 Sep;44(3):837-45
3203132
Clin Pharmacol Ther. 2007 May;81(5):768-71
17392722