C-Peptide Levels in Subjects Followed Longitudinally Before and After Type 1 Diabetes Diagnosis in TrialNet

Abstract

Insulin secretion declines rapidly after diagnosis of type 1 diabetes, followed by a slower rate of change. Previous studies have demonstrated that the C-peptide decline begins before the clinical diagnosis. Changes in insulin secretion in the same individuals studied from preclinical stages through and after clinical diagnosis have not been previously reported. RESEARCH DESIGN AND METHODSAntibody-positive relatives undergo sequential oral glucose tolerance testing (OGTT) as part of TrialNet's Pathway to Prevention study and continue both OGTT and mixed-meal tolerance testing (MMTT) as part of the Long-term Investigational Follow-up in TrialNet study if they develop type 1 diabetes. We analyzed glucose and C-peptide data obtained from 80 TrialNet subjects who had OGTT before and after clinical diagnosis. Separately, we compared C-peptide response to OGTT and MMTT in 127 participants after diagnosis. RESULTSC-peptide did not change significantly until 6 months before the clinical diagnosis of type 1 diabetes and continued to decline postdiagnosis, and the rates of decline for the first 6 months postdiagnosis were similar to the 6 months prediagnosis. There were no significant differences in MMTT and OGTT C-peptide responses in paired tests postdiagnosis. CONCLUSIONSThis is the first analysis of C-peptide levels in longitudinally monitored patients with type 1 diabetes studied from before diagnosis and continuing to the postdiagnosis period. These data highlight the discordant timing between accelerated b-cell dysfunction and the current glucose thresholds for clinical diagnosis. To preserve b-cell function, disease-modifying therapy should start at or before the acute decline in C-peptide.While it is now understood that type 1 diabetes develops over time from a genetic predisposition to the development of b-cell autoimmunity with measurable pancreatic autoantibodies (stage 1 disease) to dysglycemia (stage 2 disease) and then to a clinical diagnosis of type 1 diabetes (stage 3 disease) (1,2), little is known about sequential changes in insulin secretion and glucose homeostasis that occur as individuals progress through these stages.

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