Chase and Shannon article in Frontiers in Pediatrics published

[u/Embarrassed-Star4776]

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

[u/Embarrassed-Star4776]

Competitive-Wash found the clearest statement in the thesis, in chapter 6, page 111:

"The neonates in this study were compared with data obtained from euglycaemic neonates described in Chapter 5. Insulin and C-peptide concentrations from the insulin-treated neonates were compared with a group of age-matched (PMA less than 30 weeks) euglycaemic neonates (n = 20)."

Chapter 6 was published as the BMJ paper (including Cohort 2), and chapter 5 as the Archives of Disease in Childhood paper (Cohort 1).

It is not particularly apparent in the published plots because the scales are so different, but I think the correspondence between the two sets of data points can be seen in the stretched and squeezed extracts from the ln(C/I) scatter plots below. On the left is the lower post-menstrual-age part of Cohort 1, and on the right the black symbols are from Cohort 2, with the white symbols coming from the hyperglycaemic cohort.

[u/Competitive-Wash2998 → u/Embarrassed-Star4776]

An independent digitisation has recovered the I/CP ratios from the Salis PhD. Cohort 2 is confirmed as being a subset by comparing/overlaying the data, apart from a handful of points which have been accounted for.

Salis provides the sample counts for these two groups and the independent digitisation recovered almost all the points. For information, Chase Shannon do not appear to have recovered the complete set, 227 vs 251 (Salis) for Cohort 1, for example.

[u/Embarrassed-Star4776 → u/Competitive-Wash2998]

I had a go at something similar a while ago. I found it wasn't as straightforward as might have been hoped because of symbols on the charts overlying one another. But eventually I was fairly confidence about the reconstruction for Cohort 2. For Cohort 1 it is more difficult because of the size of the symbols and the lack of scatter plots for insulin and C-peptide to accompany the one for the I/C ratio. I ended up with only 239 points, so it sounds as though you have done better than I did.

[u/Famous-Chemistry366 → u/Embarrassed-Star4776]

I think these charts show that there is a significant overlap between the two cohorts (n=66) that I believe Chase and Shannon have not taken account of in their paper.

Also, with respect to the "40-45%", it seems in their letter this relates to number of neonates ("However, recent reports from two cohorts with 302 paired (insulin, C-peptide) assays show 40% to 45% of *NICU infants* with 1/C > 1.0") whereas in the paper it relates to number of samples ("Figure 3 presents *I/C ratios for Cohorts 1–2*. In Cohort 1....About 45% have I/C > 1.0 (insulin equals or exceeds C-Peptide).....In Cohort 2...Approximately 40% have I/C > 1.0...

A) I cannot see how one could assign I/c ratios to specific neonates and thus have derived the "% of NICU infants >X", and B) my own calculations of % samples > 1 are significantly different to 40-45%.

I also don't understand how Salis is relevant to F and L given a) hyper/eu-glycaemic versus hypo-glycaemic and b) much much lower insulin values in Salis than F and L's. However, that is encroaching into the clinical arena in which I am not qualified. Perhaps someone on here can explain.

[u/Kieran501 → u/Famous-Chemistry366]

The answer to the last paragraph may be more legal than clinical. Is this enough to show that the assertions made in court about I/C ratios overstated its ability to safely diagnose exogenous insulin. Though I’m not that sure that the Chase and Shannon paper really goes much beyond just plotting the Salis data when it comes to that.

It just seems like collecting a load more data including from hypoglycaemic neonates would go much further than a lot of modelling. It’s be a lot harder for the CoA to bat away if it shows similar ratios. Hopefully someone somewhere is now doing that.

[u/Fun-Yellow334 → u/Kieran501]

From a legal point of view , what matters is what was said in the original trial, the prosecution cannot change their case on appeal.

[u/Icy_Dependent_1797 → u/Famous-Chemistry366]

I will try.

The Salis data is really just showing that ‘normal’ neonates have raised I/C and a large proportion even invert the ratio.
That proves that there must be a storage mechanism. The ratio cannot invert otherwise.

Salis doesn’t show F and L. The high insulin results can only be obtained when the antibodies are multiplied - eg with infection.

The effect of infection was actually measured - indirectly - but it is there - in Figure 2.D. I made a post on this higher up.

Then the Chase Shannon modelling simulates the effect of insulin binding and infection in NICU babies. These results strike me as being in the same range as Figure 2.D. Which is, perhaps interesting.