Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data.
Interpretation of clinical trials to alter the decline in β-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from the Type 1 Diabetes TrialNet studies, we describe the natural history of β-cell function from shortly after diagnosis through 2 years post study randomization, assess the degree of variability between patients, and investigate factors that may be related to C-peptide preservation or loss. We found that 93% of individuals have detectable C-peptide 2 years from diagnosis. In 11% of subjects, there was no significant fall from baseline by 2 years. There was a biphasic decline in C-peptide; the C-peptide slope was -0.0245 pmol/mL/month (95% CI -0.0271 to -0.0215) through the first 12 months and -0.0079 (-0.0113 to -0.0050) from 12 to 24 months (P < 0.001). This pattern of fall in C-peptide over time has implications for understanding trial results in which effects of therapy are most pronounced early and raises the possibility that there are time-dependent differences in pathophysiology. The robust data on the C-peptide obtained under clinical trial conditions should be used in planning and interpretation of clinical trials.
Benaroya Research Institute, Seattle, Washington, USA. cjgreen@benaroyaresearch.org
Carla J
CJ
Greenbaum
Craig A
CA
Beam
David
D
Boulware
Stephen E
SE
Gitelman
Peter A
PA
Gottlieb
Kevan C
KC
Herold
John M
JM
Lachin
Paula
P
McGee
Jerry P
JP
Palmer
Mark D
MD
Pescovitz
Heidi
H
Krause-Steinrauf
Jay S
JS
Skyler
Jay M
JM
Sosenko
D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000378:metabolism*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000502:physiology; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
D002096:C-Peptide; D007328:Insulin