Longitudinal Auxological recovery in a cohort of children with Hyperinsulinaemic Hypoglycaemia

Background: Hypoglycaemia due to hyperinsulinism (HI) is the commonest cause of severe, recurrent hypoglycaemia in childhood. Cohort outcomes of HI remain to be described and whilst previous follow up studies have focused on neurodevelopmental outcomes, there is no information available on feeding and auxology. Aim: We aimed to describe HI outcomes for auxology, medications, feeding and neurodevelopmental in a cohort up to age 5 years. Method: We reviewed medical records for all patients with confirmed HI over a three-year period in a single centre to derive a longitudinal dataset. Results: Seventy patients were recruited to the study. Mean weight at birth was - 1.0 standard deviation scores (SDS) for age and sex, while mean height at 3 months was - 1.5 SDS. Both weight and height trended to the population median over the follow up period. Feeding difficulties were noted in 17% of patients at 3 months and this reduced to 3% by 5 years. At age 5 years, 11 patients (15%) had neurodevelopmental delay and of these only one was severe. Resolution of disease was predicted by lower maximum early diazoxide dose (p = 0.007) and being born SGA (p = 0.009). Conclusion: In a three-year cohort of HI patients followed up for 5 years, in spite of feeding difficulties and carbohydrate loading in early life, auxology parameters are normal in follow up. A lower than expected rate of neurodevelopmental delay could be attributed to prompt early treatment.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The study was supported by the Northern Congenital Hyperinsulinism (NORCHI) charitable fund, by the Manchester Academic Health Sciences Centre and by The University of Manchester MRC Confidence in Concept (CiC) Award (MC_PC_18056). KEC was funded by a Research Councils UK Academic Fellowship (https://www.ukri.org/). SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (105636/Z/14/Z).published version, accepted versio

Flow of endogenous and exogenous nitrogen in different segments of the small intestine in pigs fed diets with soyabean concentrate, soyabean meal or rapeseed cake.

Six barrows of an average initial BW 27.5±1.2 kg were used. Each pig was fitted with two cannulas in different segments of the small intestine: pig 1 in the duodenum (C1) and upper jejunum (C2), pig 2 in C2 and the lower jejunum (C3), pig 3 in C2 and C3, pig 4 in C1 and the terminal ileum (C4), pig 5 in C3 and C4, pig 6 in C1 and C4. Pigs were also fitted with one catheter in the vena jugularis for blood sampling and with a second one in the arteria carotis for continuous infusion of 15N-leucine (4.2 mg/kg0.75 BW/d). Pigs were used in a crossover design experiment with three treatments and three periods of digesta collection (36 h) and blood sampling (36 h). Maize starch-based diets that contained: soyabean concentrate (SC), a mixture of toasted and untoasted soyabean meal (mSBM) of a high trypsin inhibitor activity, or rapeseed cake (RC) of a high NDF content were used in the experiment. The flow of endogenous and exogenous N along the small intestine and the net reabsorption rate of endogenous N were estimated. In the C1 digesta of pigs fed on the SC, mSBM and RC diets, total N was 138, 127 and 126% of the ingested N, respectively. Sixteen, 15 and 10% of the ingested N was absorbed up to C1, and 11.1, 11.6 and 9.4 g of endogenous N (Ed-N) per kg DM intake was secreted, respectively. For corresponding diets in the C2 digesta, total N was 126, 117 and 111% of the ingested N. Thirty four, 11 and 31% of the exogenous N (Ex-N) inflow and -32, 1 and -39% of the Ed-N inflow was absorbed. In the C3 digesta, total N was 44, 47 and 43% of the ingested N, while 81, 71 and 71% of the Ex-N inflow and 54, 38 and 49% of the Ed-N inflow was absorbed, respectively. Accordingly, in the C4 digesta total N was 24, 33 and 33% of the ingested N, and 45, 43 and 4% of the Ex-N inflow was absorbed. True N digestibility at the terminal ileum was 94, 88 and 82% for the SC, mSBM and RC diets. The reabsorption rate of endogenous N before the terminal ileum was estimated as 75, 51 and 69%, respectively. It was concluded that regardless of the dietary protein source, the middle segment of the small intestine is the site of the most intense absorption of endogenous and exogenous N. Reabsorption rather than secretion of endogenous nitrogen along the pig's small intestine seems to be influenced by dietary factors