Probing the Meaning of Persistent Propeptide Release in Type 1 Diabetes
Bibliographic record
Abstract
Type 1 diabetes is well recognized to be immune mediated, resulting in destruction of β-cells. That this eradication is not always complete was evident in an early report from the Diabetes Control and Complications Trial (DCCT) showing that 11% of adult participants with type 1 diabetes for more than 5 years had measurable C-peptide in the fasting state and following mixed-meal stimulation, while no adolescents had evidence of such (1). Further, in participants with measurable C-peptide responses, C-peptide declined in all after a year of randomized therapy, with this decline being less in those who received intensive insulin therapy. Subsequently, it was shown in adolescents that 2 weeks of intensive insulin therapy, compared with conventional therapy, resulted in improved β-cell function a year later along with superior glucose control (2). In addition to C-peptide, proinsulin has also been shown to be circulating in individuals with type 1 diabetes at the time of diagnosis and to be still measurable 30 months later (3,4). Thus, there is long-standing evidence that at the time of diagnosis and subsequently, individuals with type 1 diabetes have β-cells still capable of synthesizing proinsulin, and many can process it to C-peptide and insulin. In the current issue of Diabetes Care , Sims et al. (5) report longitudinal findings on proinsulin secretion in type 1 diabetes using a large number of samples from the T1D Exchange. They divided their subjects into three groups based on stimulated C-peptide responses to a mixed meal. We have categorized these groups as having absent, intermediate, and high C-peptide responses, although the latter are a great deal lower than what is observed in healthy people. Individuals in the absent group had C-peptide responses that were below the reliable lower detection limit of the assay, and they were not studied further. These …
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.027 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.006 |
| Scholarly communication | 0.004 | 0.005 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.006 | 0.011 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".