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Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1 DIABETES CARE Sosenko, J. M., Palmer, J. P., Greenbaum, C. J., Mahon, J., Cowie, C., Krischer, J. P., Chase, H. P., White, N. H., Buckingham, B., Herold, K. C., Cuthbertson, D., Skyler, J. S. 2006; 29 (3): 643-649

Abstract

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.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.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.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.

View details for Web of Science ID 000235764100027

View details for PubMedID 16505520