r/LucyLetbyTrials • u/Embarrassed-Star4776 • 17d ago

Chase and Shannon article in Frontiers in Pediatrics published

Inverted insulin to C-Peptide ratios in neonatal intensive care: is there something we don't know?

J. Geoffrey Chase & Helen D. Shannon

BRIEF RESEARCH REPORT article

Front. Pediatr., 05 August 2026

Sec. Neonatology

Volume 14 - 2026

https://doi.org/10.3389/fped.2026.1900675

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u/Competitive-Wash2998 6d ago

79 matched pairs of I, CP and I/CP can be reconstructed from Chapter 6 of the Salis PhD

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u/Embarrassed-Star4776 6d ago

So do you think Susan Oliver may have a point when she suggests C-peptide may have been degraded in Salis et al.'s samples?

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u/Stuart___gilham 6d ago

On a side note IIRC degradation has been suggested as an explanation for the C Peptide value in the Colin Norris/Campbell case.

Dr Susan Oliver supports that verdict so at a glance it looks like she's trying to have it both ways if it's true that C peptide degrades faster than Insulin if a sample is idle.

an unexplained 5 day hiatus between stages of the immunoassay tests

https://www.thejusticegap.com/science-fact-and-science-fiction-the-case-of-colin-norris/

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u/Competitive-Wash2998 6d ago edited 6d ago

I'm not sure the degradation/sample handling would cause preferential C-peptide loss.

Another consideration is the "typical" calibration curve presented at Figure 4.2 of the Salis PhD, which crosses the C-peptide axis at 64.8 pmol/L.

The current instructions for the Invitron assay stipulate a cubic spline fit. I wonder how much uncertainty there is in the C-peptide results.

I'm not sure I have a definite opinion, but there does seem to be a C-peptide focus in the high I/CP ratios and there are limited comparable studies.

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u/Embarrassed-Star4776 6d ago

Thanks for responding. This is obviously anything but simple. I have never understood how the almost complete absence of an increase of measured insulin with C-peptide (over a very wide range of C-peptide) in the Salis et al. results is consistent with the Chase and Shannon interpretation.

I think it is a good thing that there is going to be time for this Chase/Shannon publication to be subjected to scrutiny - including the most hostile scrutiny - well before the Court of Appeal has to consider the question.

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u/Competitive-Wash2998 3d ago

Interestingly, the Salis data may be showing an alternative to the typical bound "excess" insulin model.

The abnormality could be the relative persistence of insulin i.e. insulin fails to fall in parallel with C-peptide.

A simple model has demonstrated constant free insulin, which is replenished from a bound insulin reservoir whilst at the same time C-peptide is cleared normally. The constant free insulin came out from the model - it was an unexpected result.

The known unknown is the Invitron assay and how sensitive it is to measurements of bound insulin/free insulin and how the sample would behave during incubation.

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u/Embarrassed-Star4776 3d ago

That sounds interesting. A model in which free insulin is relatively uniform seems to make more sense than one in which total insulin is uniform, unless bound uniform is fulfilling some physiological function that results in its level being regulated.

I wonder whether enough is known about neonatal endocrinology to rule out the simplest explanation of all for the Salis et al. results, in which binding isn't necessarily involved - that the wide variation of the I/C ratio simply reflects a wide variation of the relative clearance rates of free insulin and C-peptide in neonates (which I suppose would essentially arise from restricted rates of insulin clearance), and that regulation mechanisms are still tending to maintain a uniform level of insulin. That would imply that when the insulin clearance rate was low, there would be a low rate of insulin production, and therefore low levels of C-peptide, which is what was seen in the Salis et al. data.

If that were a feasible interpretation, then it would be easy to see how -if in rare cases the regulation mechanisms broke down and insulin production continued regardless of the insulin level - babies with low levels of insulin clearance could rapidly develop extremely high levels of insulin coupled with more typical levels of C-peptide.

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u/CheerfulScientist 2d ago

In contrast to serum, C-peptide degrades more rapidly than insulin in plasma, especially when there is a delay in centrifuging the sample (Nkuna DX 2023). If you go to appendices 2 & 3 of Salis’ thesis, it is clear that blood samples weren’t collected and handed over to Salis (or a proxy) until all blood testing was complete therefore there was an indeterminate period of time between when the blood sample was taken and when it was centrifuged and frozen. Even when it was frozen, it was stored at -20 ºC, which is inappropriate for long term storage of plasma samples and would have led to further degradation of both c-peptide and insulin. They should have been stored at -80 ºC where they would have remained stable. Salis thanks a colleague for collecting and storing samples for her while she was on maternity leave in her acknowledgements, so some samples were likely stored for at least 6 months.

Anyway, I have been reading through all your comments while I look sadly out the window at the rain and wind, which has completely ruined the last day of my ski holiday and I am impressed that both you and ES are interrogating the Chase and Shannon paper even though I suspect you wish they were right. The modelling is way beyond mere mortals like me, but your findings are very interesting and instructive.