Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1.
OBJECTIVE
There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis.


METHODS
Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points.


RESULTS
Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up.


CONCLUSIONS
These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.
Sosenko
Jay M
JM
Division of Endocrinology, University of Miami, PO Box 016960 (D110), Miami, FL 33101, USA. jsosenko@med.miami.edu
Palmer
Jerry P
JP
Greenbaum
Carla J
CJ
Mahon
Jeffrey
J
Cowie
Catherine
C
Krischer
Jeffrey P
JP
Chase
H Peter
HP
White
Neil H
NH
Buckingham
Bruce
B
Herold
Kevan C
KC
Cuthbertson
David
D
Skyler
Jay S
JS
D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D018450:Disease Progression; D005951:Glucose Tolerance Test; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology; D011236:Prediabetic State / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide