Diagnosis and treatment of anti-insulin antibody-mediated labile glycaemia in insulin-treated diabetes.

AIMS: Anti-insulin antibodies in insulin-treated diabetes can derange glycaemia, but are under-recognised. Detection of significant antibodies is complicated by antigenically distinct insulin analogues. We evaluated a pragmatic biochemical approach to identifying actionable antibodies, and assessed its utility in therapeutic decision making. METHODS: Forty people with insulin-treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad-specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation. RESULTS: Twenty-seven people had insulin immunoreactivity (IIR) below 3000 pmol/L that fell less than 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3000 pmol/L and fell by more than 50% after PEG precipitation. GFC demonstrated substantial high molecular weight (HMW) IIR in 7 of these 8. In this group antibodies were judged likely significant. In 2 people immunosuppression was introduced, with a good clinical result in one but only a biochemical response in another. In 6 people adjustment of insulin delivery was subsequently informed by knowledge of underlying antibody. In a final group of 5 participants IIR was below 3000 pmol/L but fell by more than 50% after PEG precipitation. In 4 of these GFC demonstrated low levels of HMW IIR and antibody significance was judged indeterminate. CONCLUSIONS: Anti-insulin antibodies should be considered in insulin-treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance. Antibody depletion may be beneficial, but conservative measures often suffice.

Familial hypocalciuric hypercalcaemia type 1 caused by a novel heterozygous missense variant in the CaSR gene, p(His41Arg): two case reports.

BACKGROUND: Familial hypocalciuric hypercalcaemia (FHH) is a rare, inherited disorder of extracellular calcium sensing. It is clinically characterised by mild to moderate parathyroid hormone dependent hypercalcaemia, an autosomal dominant pattern of inheritance, and a normal to reduced urinary calcium excretion in spite of high serum calcium. CASE PRESENTATION: We report two cases of FHH in a family caused by a novel pathogenic missense variant in the CaSR gene, p. His41Arg. Case 1, describes a 17 year old female with no significant past medical history, admitted with acute appendicitis requiring laparoscopic appendectomy and reporting a six month history of polydipsia. Routine investigations were significant for hypercalcaemia, corrected calcium 3.19 mmol/L (2.21-2.52mmol/L), elevated parathyroid hormone of 84pg/ml (15-65pg/ml) and a low 24-hour urine calcium of 0.75mmol/24 (2.50-7.50mmol/24). She was initially managed with intravenous fluids and Zolendronic acid with temporary normalisation of calcium though ultimately required commencement of Cinacalcet 30 mg daily for persistent symptomatic hypercalcaemia. Genetic analysis was subsequently positive for the above variant. Case 2, a 50-year-old female, was referred to the endocrine outpatient clinic for the management of type 2 diabetes and reported a longstanding history of asymptomatic hypercalcaemia which had not been investigated previously. Investigation revealed hypercalcaemia; corrected calcium of 2.6 mmol/L (reference range: 2.21-2.52 mmol/L); PTH of 53.7ng/L (reference range: 15-65 ng/L) and an elevated 24-hour urine calcium of 10 mmol/24 (2.50-7.50 mmol/24hr) with positive genetic analysis and is managed conservatively. Despite sharing this novel mutation, these cases have different phenotypes and their natural history is yet to be determined. Two further relatives are currently undergoing investigation for hypercalcaemia and the family have been referred for genetic counselling. CONCLUSION: Accurate diagnosis of FHH and differentiation from classic primary hyperparathyroidism can be challenging, however it is essential to avoid unnecessary investigations and parathyroid surgery. Genetic analysis may be helpful in establishing a diagnosis of FHH in light of the biochemical heterogeneity in this population and overlap with other causes of hypercalcaemia.

Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series.

BACKGROUND : Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2). METHODS: We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria. RESULTS: The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%). CONCLUSIONS: With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.

RANKL treatment of vascular endothelial cells leading to paracrine pro-calcific signaling involves ROS production.

Numerous studies have highlighted the causal link between over-production of reactive oxygen species (ROS) and cardiovascular complications such as vascular calcification (VC). Receptor-activator of nuclear factor-κB ligand (RANKL) has previously been shown to act on endothelial cells, eliciting the production/release of paracrine pro-calcific signals that act, in-turn, upon underlying vascular smooth muscle cells (VSMCs) to induce osteoblastic differentiation and VC. A role for endothelial ROS signaling in this process has not been established however. In the current paper, we investigate the possibility that RANKL leads to ROS signaling within the endothelial layer as part of the RANKL-driven VC signaling cascade. Human aortic endothelial cells (HAECs) were treated with RANKL (25 ng/ml, 72 h) and monitored for ROS production, in parallel with various pro-calcific signaling indices. Antioxidant co-treatments included TRAIL (5 ng/ml), apocynin (10 mM) and N-acetylcysteine (5 mM). Treatment of HAECs with RANKL-induced robust ROS production. This surge could be partially attenuated by TRAIL and strongly attenuated by apocynin and N-acetylcysteine. RANKL also elicited a range of signaling events in HAECs that we have previously demonstrated are coupled to osteoblastic differentiation in underlying VSMCs. These include non-canonical NF-κB/p52 activation, elevated BMP-2 release and increased alkaline phosphatase (ALP) enzyme activity (cellular and extracellular). Importantly, these RANKL-induced signaling events could be completely prevented by co-treatment of HAECs with antioxidants. In summary, RANKL elicits ROS generation in HAECs with direct consequences for generation of paracrine pro-calcific signals known to effect calcification in underlying VSMCs.

A remarkable case of thyrotoxicosis initially caused by graves' disease followed by a probable TSHoma - a case report.

BACKGROUND: Graves' disease is the commonest cause of thyrotoxicosis whilst thyrotropin (TSH)-producing pituitary adenomas (thyrotropinomas, TSHomas) are very rare and account for just 1-2% of all pituitary adenomas. Coexistence of a TSHoma and Graves' disease has been very rarely reported. Here, we report a case of a patient whose initial presentation with primary thyrotoxicosis due to Graves' disease, was subsequently followed by a relapse of thyrotoxicosis due to a probable TSHoma. CASE: A sixty-eight year old woman was referred to our department with classical features of thyrotoxicosis. Initial biochemistry confirmed hyperthyroxinaemia [free thyroxine (fT4) 20.4 pmol/L (reference range 7.0-16.0)] and a suppressed TSH [< 0.02mIU/L (0.50-4.20)]. A technetium pertechnetate uptake scan was consistent with Graves' Disease. She was treated with carbimazole for 18 months and remained clinically and biochemically euthyroid. After stopping carbimazole her fT4 started to rise but TSH remained normal. Laboratory assay interference was excluded. A TRH stimulation test demonstrated a flat TSH response and pituitary MRI revealed a microadenoma. Remaining pituitary hormones were in the normal range other than a slightly raised IGF-1. An 11C-methionine PET/CT scan coregistered with volumetric MRI (Met-PET-MRICR) demonstrated high tracer uptake in the left lateral sella region suggestive of a functioning adenoma. The patient declined surgery and was unable to tolerate cabergoline or octreotide. Thereafter, she has elected to pursue a conservative approach with periodic surveillance. CONCLUSION: This is a very unusual case of thyrotoxicosis caused by two different processes occurring in the same patient. It highlights the importance of considering dual pathology when previously concordant thyroid function tests become discordant. It also highlights a potential role of Met-PET-MRICR in the localisation of functioning pituitary tumours.

The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy.

BACKGROUND: Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11ß-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. METHODS: Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. MEASUREMENTS: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621-809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1-619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1-49] (r = - 0.42, p = 0.03), and PINP (r = - 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1-49] (r = - 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = - 0.39, p = 0.04), and OC [1-49] (r = - 0.35, p = 0.06). CONCLUSION: Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. TRIAL REGISTRATION: Irish Medicines Board Clinical Trial Number - CT900/459/1 and EudraCT Number - 2007-005018-37 . Registration date: 07-09-2007.

Clinical features and autoimmune associations in patients presenting with Idiopathic Isolated ACTH deficiency.

OBJECTIVE: Idiopathic Isolated ATCH deficiency (IIAD) is a rare cause of secondary adrenal insufficiency. As the condition is rare, and the diagnostic criteria ill-defined, there are few good clinical descriptions in the literature. We have described presenting features, autoimmune associations, natural history and responses to CRF, in a large case series of patients presenting with IIAD. DESIGN: This is a retrospective case note analysis with data derived from the recently commenced National Pituitary Database of Ireland. PATIENTS: Twenty-three patients with isolated ACTH deficiency were identified. A thorough chart and biochemistry review was performed. RESULTS: Twenty-three patients were examined (18 women and 5 men). Age at presentation ranged from 17 to 88 years, (median 48 years). Most patients complained of fatigue; 9 patients presented with hyponatraemia, 13 had autoimmune illnesses (primary hypothyroidism, n = 9). CRF stimulation testing was available in 12 of the 23 patients, 5 of whom demonstrated a rise in plasma ACTH concentrations, indicating hypothalamic, rather than pituitary aetiology. Two patients recovered ACTH secretion, and 2 patients progressed to have other pituitary hormone deficiencies. CONCLUSIONS: IIAD typically presents with insidious symptoms. Euvolaemic hyponatraemia is common at diagnosis. It is associated with autoimmune diseases, particularly primary hypothyroidism. As two patients recovered ACTH secretion, and two progressed to other pituitary hormone deficits, repeat pituitary testing should be considered, to identify recovery of function, or progression to other hormone deficits.

RANKL Inhibits the Production of Osteoprotegerin from Smooth Muscle Cells under Basal Conditions and following Exposure to Cyclic Strain.

Receptor activator of nuclear factor-κB ligand (RANKL) promotes vascular calcification, while osteoprotegerin (OPG) opposes it by blocking RANKL activity. It remains unclear which vascular cell populations produce and secrete OPG/RANKL. This study characterizes the production of OPG/RANKL from human aortic endothelial and smooth muscle cells (HAECs and HASMCs) under various conditions. HAECs and HASMCs were exposed to inflammatory stimuli (tumor necrosis factor-α or hyperglycemia) or physiological levels of hemodynamic (cyclic) strain. After 72 h, both cells and supernatant media were harvested for assessment of OPG/RANKL production. Based on initial findings, the experiments involving HASMCs were then repeated in the presence of exogenous RANKL. OPG was produced and secreted by HASMCs and (to a considerably lesser degree) HAECs under basal conditions. Inflammatory stimuli upregulated OPG production in both cell populations. Cyclic strain significantly upregulated OPG production in HASMCs. Neither cell population produced RANKL. Exposing HASMCs to exogenous RANKL inhibited basal OPG production and completely abrogated the strain-mediated upregulation of OPG. These data suggest that HASMCs are a significant source of OPG within the vasculature but that RANKL, once present, downregulates this production and appears capable of preventing the "protective" upregulation of OPG seen with HASMCs exposed to physiological levels of cyclic strain.

ALTERATIONS IN THYROID HORMONE LEVELS FOLLOWING GROWTH HORMONE REPLACEMENT EXERT COMPLEX BIOLOGICAL EFFECTS.

OBJECTIVE: Alterations in the thyroid axis are frequently observed following growth hormone (GH) replacement, but uncertainty exists regarding their clinical significance. We aimed to compare fluctuations in circulating thyroid hormone levels, induced by GH, to changes in sensitive biological markers of thyroid hormone action. METHODS: This was a prospective observational clinical study. Twenty hypopituitary men were studied before and after GH replacement. Serum thyroid-stimulating hormone (TSH), thyroid hormones, and insulin-like growth factor 1 were measured. Changes in thyroid hormone concentrations were compared to alterations in resting metabolic rate and cardiac time intervals. Health-related quality of life (QOL) was assessed by disease-sensitive and generic questionnaires. RESULTS: Following GH replacement, free thyroxine concentration declined and free triiodothyronine level increased. Resting energy expenditure increased, particularly in subjects with profound hypopituitarism, including TSH deficiency (16.73 ± 1.75 kcal/kg/min vs. 17.96 ± 2.26 kcal/kg/min; P = .01). Alterations in the thyroid axis were more pronounced in subjects with a low/normal baseline respiratory quotient (RQ) who experienced a paradoxical rise in RQ (0.81 vs. 0.86; P = .01). Subjects with a high baseline RQ experienced a slight but nonsignificant fall in RQ without alteration in thyroid axis. The isovolumetric contraction time was shortened during the study; however, this did not reach statistical significance. Improvements in QOL were observed despite alterations in thyroid axis. CONCLUSION: Changes in the thyroid axis following GH replacement are associated with complex tissue-specific effects. These fluctuations may induce a hypothyroid phenotype in some tissues while appearing to improve the biological action of thyroid hormone in other organs. ABBREVIATIONS: AGHDA = Assessment of Growth Hormone Deficiency in Adulthood; CHOox = carbohydrate oxidation; ET = ejection time; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; GHD = growth hormone deficiency; HB-RQ = high baseline respiratory quotient; HPT = hypothalamic-pituitary-thyroid; ICT = isovolumetric contraction time; IGF-1 = insulin-like growth factor 1; IRT = isovolumetric relaxation time; LB-RQ = low baseline respiratory quotient; LV = left ventricular; NHP = Nottingham Health Profile; QOL = quality of life; REE = resting energy expenditure; RQ = respiratory quotient; rT3 = reverse triiodothyronine; SF-36 = Short Form 36; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; TT3 = total triiodothyronine; TT4 = total thyroxine.

DIFFERENTIAL REGULATION OF 11ß-HYDROXYSTEROID DEHYDROGENASE TYPE 1 ACTIVITY IN PATIENTS WITH DIFFERING ETIOLOGIES OF HYPOPITUITARISM.

OBJECTIVE: Pituitary patients with different etiologies of hypopituitarism exhibit differing phenotypes, despite similar replacement therapy strategies. We hypothesized that differential regulation of the isoenzyme 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), which mediates the net autocrine conversion of cortisone to cortisol in adipose tissues and liver, may play a role. METHODS: We studied 11ß-HSD1 activity (using urine cortisol/cortisone metabolites ratio) in 36 hypopituitary patients with treated craniopharyngiomas, treated remitted Cushing disease, and treated nonfunctioning pituitary adenomas + prolactinomas on and off growth hormone (GH) replacement. RESULTS: 11ß-HSD1 activity was higher in subjects with craniopharyngioma both on and off GH, as evidenced by increased tetrahydrocortisol to tetrahydrocortisone metabolite ratios compared to other diagnostic groups, but there was no difference in body mass index, insulin levels, serum hormone measurements, or hydrocortisone dose between groups. CONCLUSION: Craniopharyngiomas are associated with enhanced 11ß-HSD1 activity compared to other diagnostic hypopituitary groups, and this may contribute to the adverse phenotypic and metabolic features seen in this condition. ABBREVIATIONS: BMI = body mass index; Em = cortisone metabolites; Fm = cortisol metabolites; GH = growth hormone; 11ß-HSD1 = 11ß-hydroxysteroid dehydrogenase type 1; IGF-1 = insulin-like growth factor 1; NFPA = nonfunctioning pituitary adenoma; THE = tetrahydrocortisone; THF = tetrahydrocortisol.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

OBJECTIVE: Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. DESIGN: A prospective, observational study of patients receiving GH replacement as part of routine clinical care. PATIENTS: Twenty adult hypopituitary men. MEASUREMENTS: Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. RESULTS: The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. CONCLUSIONS: In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle.

Utility of repeat cytological assessment of thyroid nodules initially classified as benign: clinical insights from multidisciplinary care in an Irish tertiary referral centre.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is the tool of choice for evaluating thyroid nodules with the majority classified as benign following initial assessment. However, concern remains about false negative results and some guidelines have recommended routine repeat aspirates. We aimed to assess the utility of routine repeat FNAB for nodules classified as benign on initial biopsy and to examine the impact of establishing a multidisciplinary team for the care of these patients. METHODS: We performed a retrospective review of 400 consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our hospital between July 2008 and July 2011. Data recorded included demographic, clinical, histological and radiological variables. RESULTS: Three hundred and fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of routine repeat biopsy increased significantly over the time course of the study (p for trend = 0.012). Nine Thy 2 nodules were classified differently on the basis of routine repeat biopsy; one patient was classified as malignant on repeat biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified as a follicular lesions on repeat biopsy-six diagnosed as benign following lobectomy; two declined lobectomy and were followed radiologically with no nodule size increase. CONCLUSIONS: The false negative rate of an initial benign cytology result, from a thyroid nodule aspirate, is low. In the setting of an experienced multidisciplinary thyroid team, routine repeat aspiration is not justified.

Newly diagnosed T1 diabetes presenting with hypoglycemia due to simultaneous co-existence of Addison disease.

Type 1 diabetes mellitus (TIDM) classically presents with symptomatic hyperglycemia and many patients develop diabetic ketoacidosis prior to their diagnosis. However, non-classical presentation or co-presentation with associated diseases may delay diagnosis or lead to challenges in acute, clinical management. An 18-yr-old girl presented to hospital with severe, symptomatic hypoglycemia. Clinical history and serum electrolyte concentrations suggested a diagnosis of adrenal insufficiency. She remained hypoglycemic until glucocorticoid replacement was commenced, at which point she developed persistent hyperglycemia requiring insulin therapy. Subsequent follow up confirmed the diagnosis of Addison's disease (AD), the treatment of which unmasked co-existing type 1 diabetes. Autoimmune diseases often cluster together in affected patients and first-degree relatives. Approximately 1 in 200 patients with T1DM develop AD. However, months or more commonly years usually elapse between the presentation of different autoimmune conditions. The co-diagnosis T1DM and AD in the acute setting is rare. Moreover, the first presentation of T1DM with severe hypoglycemia is even more exceptional. This case highlights the need for vigilance during the acute, emergency management of patients with autoimmune conditions and, in particular, to consider the possibility of concurrent antibody-mediated diseases which may need to be addressed during resuscitation.

What's distressing about having type 1 diabetes? A qualitative study of young adults' perspectives.

BACKGROUND: Diabetes distress is a general term that refers to the emotional burdens, anxieties, frustrations, stressors and worries that stem from managing a severe, complex condition like Type 1 diabetes. To date there has been limited research on diabetes-related distress in younger people with Type 1 diabetes. This qualitative study aimed to identify causes of diabetes distress in a sample of young adults with Type 1 diabetes. METHODS: Semi-structured interviews with 35 individuals with Type 1 diabetes (23-30 years of age). RESULTS: This study found diabetes related-distress to be common in a sample of young adults with Type 1 diabetes in the second phase of young adulthood (23-30 years of age). Diabetes distress was triggered by multiple factors, the most common of which were: self-consciousness/stigma, day-to-day diabetes management difficulties, having to fight the healthcare system, concerns about the future and apprehension about pregnancy. A number of factors appeared to moderate distress in this group, including having opportunities to talk to healthcare professionals, attending diabetes education programmes and joining peer support groups. Young adults felt that having opportunities to talk to healthcare professionals about diabetes distress should be a component of standard diabetes care. CONCLUSIONS: Some aspects of living with diabetes frequently distress young adults with Type 1 diabetes who are in their twenties. Clinicians should facilitate young adults' attendance at diabetes education programmes, provide them with opportunities to talk about their diabetes-related frustrations and difficulties and, where possible, assist in the development of peer-support networks for young adults with diabetes.

Considering quality of care for young adults with diabetes in Ireland.

BACKGROUND: Research on the quality of diabetes care provided to young adults with Type 1 diabetes is lacking. This study investigates perceptions of quality of care for young adults with Type 1 diabetes (23-30 years old) living in the Republic of Ireland. METHODS: Thirty-five young adults with Type 1 diabetes (twenty-nine women, six men) and thirteen healthcare professionals (ten diabetes nurse specialists, three consultant Endocrinologists) were recruited. All study participants completed semi-structured interviews that explored their perspectives on the quality of diabetes services in Ireland. Interviews were analyzed using standard qualitative thematic analysis techniques. RESULTS: Most interviewees identified problems with Irish diabetes services for young adults. Healthcare services were often characterised by long waiting times, inadequate continuity of care, overreliance on junior doctors and inadequate professional-patient interaction times. Many rural and non-specialist services lacked funding for diabetes education programmes, diabetes nurse specialists, insulin pumps or for psychological support, though these services are important components of quality Type 1 diabetes healthcare. Allied health services such as psychology, podiatry and dietician services appeared to be underfunded in many parts of the country. While Irish diabetes services lacked funding prior to the recession, the economic decline in Ireland, and the subsequent austerity imposed on the Irish health service as a result of that decline, appears to have additional negative consequences. Despite these difficulties, a number of specialist healthcare services for young adults with diabetes seemed to be providing excellent quality of care. Although young adults and professionals identified many of the same problems with Irish diabetes services, professionals appeared to be more critical of diabetes services than young adults. Young adults generally expressed high levels of satisfaction with services, even where they noted that aspects of those services were sub-optimal. CONCLUSION: Good quality care appears to be unequally distributed throughout Ireland. National austerity measures appear to be negatively impacting health services for young adults with diabetes. There is a need for more Endocrinologist and diabetes nurse specialist posts to be funded in Ireland, as well as allied health professional posts.

Differences in the structure of outpatient diabetes care between endocrinologist-led and general physician-led services.

BACKGROUND: Despite a shift in diabetes care internationally from secondary to primary care, diabetes care in the Republic of Ireland remains very hospital-based. Significant variation in the facilities and resources available to hospitals providing outpatient diabetes care have been reported in the UK. The aim of this study was to ascertain the structure of outpatient diabetes care in public hospitals in the Republic of Ireland and whether differences existed in services provided across hospitals. METHODS: We conducted a cross sectional observational study of the 36 public general hospitals providing adult outpatient diabetes care in the Republic of Ireland. Data relating to numbers of specialist medical, nursing and allied health professionals, waiting times for new and return patients, patterns of discharge back to primary care and engagement in quality improvement initiatives were recorded. RESULTS: Thirty-five of the 36 eligible hospitals participated in the study. Sixty percent of these had at least one consultant endocrinologist in post, otherwise care delivery was led by a general physician. Waiting times for newly diagnosed patients exceeded six months in 30% of hospitals and this was higher where an endocrinologist was in place (47% V 7%, p = 0.013). Endocrinologists were more likely to have developed subspecialty clinics, access to allied health professionals and engage more in quality improvement initiatives but less likely to discharge patients back to primary care than general physicians (76 v 29%, p = 0.005). CONCLUSIONS: Variations exist in the structure and provision of diabetes care in Irish hospitals. Endocrinology-led services have more developed subspecialty structures and access to specialist allied health professionals and engage more in quality improvement initiatives. Nonetheless, waiting times are longer and discharge rates to primary care are lower than for non-specialty led services. Further studies to determine the extent to which case-mix variation accounts for these observations are warranted. Aspects of hospital-based outpatient care could be developed further to ensure equitable services are provided nationally. At a time when the delivery of diabetes services in primary care is being promoted, further research is warranted on the factors influencing the successful transition to primary care.

Dealing with the devil: weight loss concerns in young adult women with type 1 diabetes.

AIMS AND OBJECTIVES: To examine the weight loss concerns of young adults with type 1 diabetes. BACKGROUND: Eating disorders are prevalent in young women with type 1 diabetes. DESIGN: Qualitative. METHODS: Interviews with 35 young adults (23-30 years of age) with type 1 diabetes and 13 healthcare professionals. RESULTS: Most female interviewees were concerned about the difficulties of losing weight when having diabetes. Six female interviewees developed severe eating disturbances when they were younger. These women initially regarded their disturbed eating behaviour positively and engaged in weight loss activities intermittently. However, over time, they lost control of their behaviour, and it came to dominate their lives. Family conflict often intensified disordered eating behaviours. Eventually all of these women managed to transition away from their behaviour, although this process took, for some of them, several years. Several of them (now in their early to late twenties), however, continued to struggle with weight loss impulses. Healthcare professionals felt that eating- and weight-related issues often went undiagnosed and undocumented in young adult women with type 1 diabetes. CONCLUSION: Many young women with type 1 diabetes are worried about their weight, but will not engage in risky weight loss activities because of concerns about their health. A minority of young adult women will develop more severe eating-related disturbances. These eating disturbances may last a significant amount of time before clinicians become aware of them. These women may also experience disordered weight loss impulses for sometime after clinical interventions. RELEVANCE TO CLINICAL PRACTICE: Clinicians should screen young adult women with type 1 diabetes for eating disorders and monitor young adult women who have developed eating disorders over the longer term. There may be a need to provide asymptomatic young women with diabetes with information about the potential risks of insulin omission.

Real-world outcomes of continuous glucose monitoring in adults with diabetes mellitus attending an Irish tertiary hospital.

BACKGROUNDS AND AIMS: The American Diabetes Association/European Association for the Study of Diabetes recently recommend the preferential use of continuous glucose monitoring(CGM) over self-monitoring of blood glucose for the management of type 1 diabetes (T1DM). For most adults with T1DM, the recommended target time in range is > 70% with < 4% time below range. In Ireland, CGM use has become increasingly popular since 2021. We aimed to audit adult CGM use and analyse CGM metrics in our cohort of adults with diabetes attending a tertiary diabetes centre. METHODS: People with diabetes who were using DEXCOM G6 CGM devices, and sharing their data with the healthcare team on the DEXCOM CLARITY for healthcare professionals platform were included in the audit. Clinical information, glycated haemoglobin (HbA1c) and CGM metrics were gathered retrospectively from medical records and the DEXCOM CLARITY platform. RESULTS: Data were available for 119 CGM users, 96.9% with T1DM, median age 36 years (IQR = 20) and median diabetes duration 17 years (IQR = 20). Fifty-three per cent of the cohort was male. Mean time in range was 56.2% (SD = 19.2) and mean time below range was 2.3% (SD = 2.6). Mean HbA1c in CGM users was 56.7 mmol/mol (SD = 13.1). This represented a decrease of 6.7 mmol/mol compared to the last HbA1c measurements available pre-commencement of CGM (p ≤ 0.0001, CI 4.4-8.9). The percentage of people in this cohort with a HbA1c < 53 mmol/mol was 40.6% (n = 39/96), compared to 17.5% (n = 18/103) pre-commencement of CGM. CONCLUSIONS: Our study highlights the challenges in optimising the use of CGM. Our team aims to focus on providing additional education to CGM users, more frequent touch-base virtual reviews and increasing access to hybrid closed-loop insulin pump therapy.

Acute Charcot arthropathy as a first presentation of type 2 diabetes mellitus.

Charcot arthropathy in people with diabetes is generally seen when diabetes has been well established, and therefore it is not routinely considered as a differential diagnosis in people presenting with erythematous and oedematous joints in primary care. We present two cases of acute Charcot arthropathy as a first presentation of type 2 diabetes mellitus. The first case describes a man in his 70s, who presented with a 5-week history of right foot pain, treated initially in the community as cellulitis. A diagnosis of acute Charcot arthropathy was made in the emergency department following review by the orthopaedic and podiatry department. The second case describes a woman in her 40s who presented with a 2-week history of ankle pain. Charcot arthropathy is associated with significant morbidity and mortality, and these cases highlight the importance of including Charcot arthropathy in the differential diagnosis when people present with atypical joint swelling.