Award winners show high standard of endocrinological research in Ireland

The winners of the awards at the Irish Endocrine Society (IES) Annual Meeting 2023 demonstrated the strength and variety of the research being undertaken in the specialty in Ireland. IES President Prof Fidelma Dunne told the Medical Independent the standard of this research has risen “significantly” over the past decade.

“You can see that in the presentations,” Prof Dunne, who is Consultant Endocrinologist in Saolta University Health Care Group, and Professor of Medicine at the University of Galway, said.

“They are all of a very high standard scientifically, and also in the way they are presented.”

The O’Donovan medal for the best oral presentation was awarded to Mr Reece Corbett, PhD researcher, Ulster University, Coleraine, Northern Ireland. The title of the study was ‘Once-daily oral administration of GPR120 agonist Compound A improves pancreatic islet and β-cell health through actions on the small intestine’. The long-chain FFA receptor, GPR120 (FFAR4) has received interest for the treatment of type 2 diabetes (T2D). “Further research is needed in identifying novel synthetic agonists with greater efficacy,” according to the research team.

One such agonist, Compound A, has shown potential due to its high selectivity (EC50=0.35µM). For the study, high-fat-fed (HFF) C57BL/6 mice were treated with a daily oral dose of Compound A (0.1μmol/kg) alone or in combination with sitagliptin (50mg/kg) for 21 days. After long-term treatment of obese-diabetic mice, metabolic effects, islet morphology, tissue gene (qPCR) and protein (immunohistochemistry) expression, insulin sensitivity, and glucose tolerance were assessed.

“Compound A is a viable treatment for T2D, as GPR120 agonism has beneficial effects on β-cells, mediated by GLP-1 from gastrointestinal L-cells, and in combination with sitagliptin reduces stress on L-cells through decreased demand for GCG gene expression,” according to the researchers.

PCOS

The Montgomery medal for the best poster presentation was awarded to Dr Tara McDonnell, RCSI, and Beaumont Hospital, Dublin. The study conducted by Dr McDonnell and the research team was entitled ‘Clinical and metabolic phenotyping of a large prospective cohort of Irish women with polycystic ovary syndrome (PCOS): The relationship between insulin sensitivity and serum classic and 11-oxygenated androgens’.

Serum 11-oxygenated androgens constitute the bulk of circulating androgens in women with PCOS; however, their relationship with metabolic disease remains unclear. The researchers aimed to delineate the relationship between circulating androgens and metabolic risk in a large prospective Irish cohort. They conducted standardised phenotyping, including anthropometric measurements, metabolic assessment and serum steroid profiling. Androgens were measured by immunoassay in all patients; serum multi-steroid profiling for classic and 11-oxygenated androgens by liquid chromatography tandem mass 67 spectrometry (LC-MS/MS) was performed in a subset of PCOS patients. The relationship between insulin sensitivity, body composition and androgens was assessed by Spearman correlation testing and linear regression analysis. A total of 118 participants with PCOS (median age 28.3 [IQR 26-33]; median BMI 32.6 [IQR 26.1-38.7]); and 40 control women were studied.

“This carefully phenotyped cohort highlights the complex relationship between androgens and insulin sensitivity in women with PCOS,” according to the research team.

“Future studies are required to dissect the mechanisms linking androgen excess with metabolic disease in this population.”

Diabetic ketoacidosis

The Jennings medal for the best presentation in paediatrics was awarded for the study ‘A decade of diabetic ketoacidosis (DKA) at type 1 diabetes (T1D) diagnosis in children and young people nationally by Sláintecare region’. The study was led by Prof Edna Roche, Professor in Paediatrics at Trinity College Dublin, and Consultant Paediatrician and Paediatric Endocrinologist at Children’s Health Ireland at Tallaght University Hospital, Dublin.

DKA is a life-threatening complication of T1D. Increasingly DKA at diabetes onset is associated with adverse long-term metabolic outcomes. The objective of this study was to report the proportion, age, and severity of DKA at diabetes onset in children aged under 15 years of age (2011-2021) nationally by healthcare region. The Irish Childhood Diabetes National Register (ICDNR) is a prospective incidence register which monitors the frequency, clinical, laboratory and demographic characteristics of T1D in those under 15 years at diagnosis. Incident cases were categorised by year, age and severity using the International Society for Paediatric and Adolescent Diabetes definition of DKA. Participating centres were grouped into Sláintecare regions. Nationally in the period (2011-2021), there were 3,186 ICDNR registered incident cases of T1D. Biochemical data were available to define DKA status for 2,888 (90.6 per cent) of the cohort. Overall, 37.3 per cent of children presented in DKA of whom 16-to-27 per cent had moderate or severe DKA. The proportion presenting in DKA varied over time and by region. The proportion of children presenting in DKA within age groups was highest in the 10-to-14.99 year (41.2 per cent) and 0-to-4.99 year (39.3 per cent) ranges, and lowest in the five-to-9.99 (31.6 per cent) year group.

“Ireland has a high incidence of type 1 diabetes and unacceptably high rates of DKA at presentation in those under 15 years,” according to the study’s conclusion.

“These national register data provide important information to guide interventions to reduce the frequency of life-threatening DKA in our population.”

AR-NKGCD

Dr Claire Reynolds, Children’s Health Ireland at Crumlin, Dublin, received the award for best case report. The title of the study was ‘MCM4 deficiency causing natural killer (NK) and glucocorticoid deficiency with DNA repair defect (AR-NKGCD): Experience from the Irish Traveller community’.

A new condition, autosomal recessive natural killer and glucocorticoid deficiency (AR-NKGCD) was first described in Irish Travellers in 2008. It was attributed to recessive mutations in MCM4/PRKDC gene in 2012. AR-NKGCD is characterised by short stature, glucocorticoid and NK cell deficiency, and is a disorder of DNA repair.

“Experience of the condition has expanded at our centres, as more cases have been confirmed,” according to the research team.

Data from available medical, laboratory, genetic and radiology records on patients over the past 10 years was compiled. Sequencing analysis of intron 1 of the MCM4/PRKDC gene in all patients (n=19) revealed the presence of the c71-2A>G p.(Phe24Argfs) mutation in the homozygous state. In those for whom data was available, all were born small for gestational age, birth weight between 0.4th – 2nd centiles. In addition, all had delayed bone age, short stature, and low weight. Most children had mild dysmorphic features. Feeding difficulties, failure to thrive and recurrent infections were observed in infancy and young childhood. Fatigue, hyperpigmentation, and development delay were also observed. Over 60 per cent required corticosteroid replacement (hydrocortisone doses range 9-to-15mg/m²). In others only emergency treatment was recommended. Mineralocorticoid secretion was not impaired. Over 80 per cent had raised ACTH levels. A serious adrenal crisis following infection occurred in three patients.

“AR-NKGCD is a rare disorder with a variable phenotype,” according to the research team.

“There is an increased risk of primary adrenal insufficiency, adrenal crisis, infection, malignancies, and premature death. Input from endocrinology and immunology specialists is required.”

Quality measures in diabetes

Finally, ‘Quality measures in the diabetes clinic’ was the title of research that won the award for the best audit or quality improvement project. It was conducted by researchers in University Hospital Limerick (UHL). The United States National Committee for Quality Assurance (NCQA) describes specific clinical process and outcome measures to promote the use of a performance measurement set for diabetes services. An audit of 106 consecutive adult attendances was conducted at UHL’s diabetes clinic using these measures against specified NCQA targets and a total weighted score.

Blood pressure control met the standard, while HbA1c control and lipid control did not. Neither nephropathy nor retinal assessment met targets, while foot assessment did.

“As measured against NCQA standards, our clinic did not reach desired targets,” according to the UHL researchers.

“Focused practical or educational solutions may improve measures on reaudit,” according to the researchers.

“Further evaluation is needed to determine if US-NCQA standards are applicable to an Irish tertiary care setting, particularly with most recent guidelines.”