Diabetes care and pregnancy outcomes for women with pregestational diabetes in Ireland.

AIMS: Pre-gestational diabetes mellitus (PGDM) is associated with adverse outcomes. We aimed to examine pregnancies affected by PGDM; report on these pregnancy outcomes and compare outcomes for patients with type 1 versus type 2 diabetes mellitus; compare our findings to published Irish and United Kingdom (UK) data and identify potential areas for improvement. METHODS: Between 2016 and 2018 information on 679 pregnancies from 415 women with type 1 Diabetes Mellitus and 244 women with type 2 diabetes was analysed. Data was collected on maternal characteristics; pregnancy preparation; glycaemic control; pregnancy related complications; foetal and maternal outcomes; unscheduled hospitalisations; congenital anomalies and perinatal deaths. RESULTS: Only 15.9% of women were adequately prepared for pregnancy. Significant deficits were identified in availability and attendance at pre-pregnancy clinic, use of folic acid, attaining appropriate glycaemic targets and appropriate retinal screening. The majority of pregnancies (n = 567, 83.5%) resulted in a live birth but the large number of infants born large for gestational age (LGA) (n = 280, 49.4%), born prematurely <37 weeks and requiring neonatal intensive care unit (NICU) admission continue to be significant issues. CONCLUSIONS: This retrospective cohort study identifies multiple targets for improvements in the provision of care to women with pre-gestational DM which are likely to translate into better pregnancy outcomes.

The Presentation and Diagnosis of the First Known Community-Transmitted Case of SARS-CoV-2 in the Republic of Ireland.

Introduction This case series describes the diagnosis of the first case of community transmission of SARS-CoV-2 in the Republic of Ireland. Cases Case 1: A 25 year old male presented with dyspnoea, cough and high fevers for 4 days. He was commenced on broad-spectrum antimicrobials and oxygen therapy. His respiratory function deteriorated in spite of these measures and he required mechanical ventilation. CT showed left upper lobe consolidation as well as multifocal ground-glass opacification. Case 2: A 43 year-old male presented with headache and was found incidentally to have pneumonia. He was recently diagnosed with pituitary apoplexy secondary to an adenoma with resultant pituitary insufficiency but MRI brain was stable. His respiratory function deteriorated in spite of antibiotics and he required mechanical ventilation. CT showed likely atypical infection with resultant ARDS. Outcome Both underwent nasopharyngeal RT-PCR testing for SARS-CoV-2. Patient 2 was positive. Patient 1 was extubated and made a good recovery. Patient 2 was transferred to another centre for ECMO therapy. He died 27 days after transfer. Conclusion Given the atypical presentations in generally otherwise young and healthy individuals, the decision was made outside of national guidance to perform testing for SARS-CoV-2. This diagnosis had far-reaching implications for the SARS-CoV-2 pandemic within Ireland.

An Irish National Diabetes in Pregnancy Audit: aiming for best outcomes for women with diabetes.

AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.

First reported case in Ireland of MEN2A due to a rare mutation in exon 8 of the RET oncogene.

UNLABELLED: We present the case of a 30-year-old female who was diagnosed with hereditary phaeochromocytoma secondary to a rare gene mutation in exon 8 of the RET oncogene. This genetic mutation was picked up as part of an extended genetic screen using a method known as next generation sequencing. Detection of this genetic mutation prompted further screening for the manifestation of multiple endocrine neoplasia type 2A (MEN2A). The patient subsequently underwent a thyroidectomy with histology confirming C-cell hyperplasia. LEARNING POINTS: Genetic analysis is an important step in the diagnostic work up of phaeochromocytoma.Extended genetic analysis is important when there is a strong suspicion of hereditary phaeochromocytoma.Mutations in exon 8 of the RET gene are associated with phaeochromocytoma as part of MEN2A syndrome.

Gastric pacing for diabetic gastroparesis--does it work?

The management of diabetic gastroparesis resistant to medical therapy is very difficult Gastric electrical stimulation (GES) is a relatively new therapeutic modality which has shown some promise in international trials. It has seen use in four patients in Ireland. Our aim was to determine if GES improved patients' outcomes in terms of duration and cost of inpatient stay and glycaemic control. We reviewed the patients' case notes and calculated the number of days spent as an inpatient with symptomatic gastroparesis pre and post pacemaker, the total cost of these admissions, and patients' average HbA1c pre and post GES. Mean length of stay in the year pre GES was 81.75 days and 62.25 days in the year post GES (p=0.89). There was also no improvement in glycaemic control following GES. GES has been ineffective in improving length of inpatient stay and glycaemic control in our small patient cohort.

Isolated acquired ACTH deficiency and primary hypothyroidism: a short series and review.

Idiopathic isolated ACTH deficiency, congenital or acquired, is rare. It may be found in association with primary hypothyroidism. Here we describe four cases of acquired idiopathic isolated ACTH deficiency illustrating its importance and variable presentation. All cases had a structurally normal pituitary gland and persistently normal residual pituitary function. Three cases had co-existing primary hypothyroidism. We discuss the protean presentation of this rare but important condition, its treatment, associations, and possible aetiologies.

Periodontitis and type 2 diabetes: is oxidative stress the mechanistic link?

Periodontitis is a common, chronic inflammatory disease initiated by bacteria which has an increased prevalence and severity in patients with type 2 diabetes. Recent studies indicate that the co-morbid presence of periodontitis can, in turn, adversely affect diabetic status and the treatment of periodontitis can lead to improved metabolic control in diabetes patients. Current evidence points to a bidirectional interrelationship between diabetes and inflammatory periodontitis. The importance of oxidative stress-inflammatory pathways in the pathogenesis of type 2 diabetes and periodontitis has recently received attention. Given the bidirectional relationship between these two conditions, this review discusses the potential synergistic interactions along the oxidative stress-inflammation axis common to both type 2 diabetes and periodontitis, and the implications of this relationship for diabetic patients.

ABLE - assessment based learning.

Over the past decade the Australian health care system has moved rapidly toward a greater emphasis on medical care being provided within the community. This trend can only continue as our population ages and levels of chronic and complex illness continue to rise. Primary care now includes: a higher proportion of general practitioners working in group practices supported by practice nurses and allied health professionals- both on site and in the community, increased patient presentations for chronic and complex disease - often compounded by mental health and social issues, and, more hospital in the home, early discharge and similar programmes enabling shared management of sicker patients in the community.

Attitudes, awareness and oral health-related quality of life in patients with diabetes.

The purpose of this study was to assess the knowledge diabetic patients have of their risk for periodontal disease, their attitude towards oral health and their oral health-related quality of life (OHRQL). One hundred and one consecutive patients (age range 31-79 years) recruited from a diabetic outpatient clinic participated in the study. Twenty-seven per cent of participants had type 1 diabetes, 66% type 2 and 7% did not know what type of diabetes they had. The length of time since participants were diagnosed as diabetic ranged from 1 to 48 years. Metabolic control of diabetes as determined by HbA1c levels ranged from 6.2% to 12.0% compared with the normal range of 4.5-6.0%. Thirty-three per cent of participants were aware of their increased risk for periodontal disease, 84% of their increased risk for heart disease, 98% for eye disease, 99% for circulatory problems and 94% for kidney disease. Half of the participants who were aware of their increased risk for periodontal disease had received this information from a dentist. Dental attendance was sporadic, with 43% reporting attendance within the last year. OHRQL was not significantly affected by the presence of diabetes in the group surveyed, in comparison with a previous survey of non-diabetic patients. A significant association was found between metabolic control and dentate status. Awareness of the potential associations between diabetes, oral health and general health needs to be increased in diabetic patients.

The cost of treating type 2 diabetes (CODEIRE).

Diabetes mellitus is the most common chronic metabolic disease and a major source of morbidity and mortality. Type 2 diabetes (T2D) is by far the most prevalent form of diabetes accounting for around 90% of cases worldwide. In recent years it has become apparent that a diabetes epidemic is unfolding as a result of increasing obesity, sedentary lifestyles and an ageing population. The enormity of the diabetes epidemic raises concern about the total cost to healthcare systems. This study was undertaken to investigate the direct healthcare costs of managing T2D in Ireland. Data was captured on 701 diabetes patients attending four diabetes centres. A bottom-up, prevalence-based design was used, which collected data on hospital resource use and clinical outcome measures over a 12-month period (1999/2000). The study was observational in nature, focusing on usual care of patients with T2D. Although the true prevalence of T2D in Ireland is unknown, conservative estimates are 3.9% for diagnosed diabetes and 6% for both diagnosed and undiagnosed diabetes. Using these figures the annual total direct cost was estimated at 377.2 million euro for diagnosed diabetes and 580.2 million euro for both diagnosed and undiagnosed diabetes. This corresponds to 4.1% and 6.4% of total healthcare expenditure respectively. Hospitalisations were the main driver of costs, accounting for almost half of overall costs, while ambulatory and drug costs accounted for 27% and 25% respectively. Hospitalisation costs were high because 60% of patients had developed complications. The most common microvascular and macrovascular complications were neuropathy and angina respectively. The annual cost of care for patients with microvascular and macrovascular complications were 1.8 and 2.9 times the cost of treating those without clinical evidence of complications respectively. The figure for patients with both types of complications was 3.8. This study shows that T2D is a very costly disease, largely due to the cost of and the management of complications. Many diabetes related complications are preventable, therefore it would appear a cost-effective approach for government to invest in the prevention of T2D and diabetes related complications.

Gastric electrical stimulation: a report of two cases.

Gastroparesis refractory to prokinetic agents poses a major challenge to the physician and patient, alike. In the past 5 years, electrical methods to treat gastroparesis have emerged from animal and human experiments to a potentially valuable tool in clinical gastroenterology. One of these methods, known as gastric electrical stimulation (GES), is being increasingly used in specialized centres worldwide, but had never been tried in Ireland. We describe here our experience with the first two implantations of gastric neurostimulators performed in Ireland and the outcome with these 2 patients. Our results at 6 months show reduction in symptoms and improvement in quality of life, which is encouraging and should prompt further evaluation of GES for patients with gastroparesis refractory to medical therapy.

Rationalising the design of polymeric thermoresponsive biomaterials.

We investigated the cell adhesion and growth of a series of thermoresponsive copolymers of N-isopropylacrylamide (NIPA) and N-tert-butylacrylamide (NtBA) above their lower critical solubility temperatures (LCST). It was found that cell adhesion and growth on the solvent cast films improved with increasing the NtBA content in the copolymers. The improvement was dependent on cell line. The surfaces of copolymers were analysed by atomic force microscopy. The topography of polymer films was not dependent on composition. The differences in the cell attachment and growth were attributed to the variation of surface energy with composition. The surface energy of copolymers decreased with the increase in the NtBA content. We conclude that poly(N-isopropylacrylamide) (poly(NIPA)) is a relatively poor substrate for cell growth and proliferation. However, its ability to support cell growth can be significantly improved by suitable modification.

Prevalence and lifestyle determinants of the metabolic syndrome.

Participants with the metabolic syndrome are at risk of developing type 2 diabetes and coronary heart disease. The aim of this study was to determine the role of lifestyle risk factors in the development of the metabolic syndrome with particular reference to physical activity, smoking and alcohol consumption. We performed a cross sectional study of the prevalence of CVD risk factors and glucose intolerance, including type 2 diabetes involving a group of 1473 men and women were sampled from 17 general practice lists in the South of Ireland. A total of 1018 attended for screening, giving a response rate of 69%. Participants completed a detailed health and lifestyle questionnaire and provided fasting blood samples for analysis of glucose, insulin and lipids. The metabolic syndrome was defined according to the current WHO criteria. The prevalence of the metabolic syndrome was 21.0% (95% C.I. 18.7% to 24.1%). In multivariate analyses with the metabolic syndrome as the dependent variable we observed a significant, independent inverse association with physical activity level (OR = 0.60; 95% CI, 0.39-0.90 for medium and OR = 0.51; 95% CI, 0.28-0.93) for high level of activity relative to the low level of activity group). Ex-drinkers had a higher prevalence of the syndrome in multivariate analysis relative to occasional drinkers, (OR = 2.38; 95% CI, 1.08-5.26). Prevalence of the metabolic syndrome was not significantly associated with current alcohol consumption or with smoking status. These data highlight the importance of physical inactivity in the aetiology of the metabolic syndrome.

Alcohol intake and insulin resistance. A cross-sectional study.

BACKGROUND AND AIM: The development of insulin resistance is a critical step in the pathogenesis of type 2 diabetes. The effect of alcohol intake on insulin sensitivity/resistance is not well defined. The aim of this study was to examine the association between alcohol intake and insulin resistance in a sample of middle-aged men and women with data on a wide range of potential confounding factors, including diet. METHODS: We performed a cross sectional study involving a group of 1018 men and women, sampled from 17 general practice lists in the South of Ireland, with a response rate of 69%. Participants completed a detailed health and lifestyle questionnaire and a food frequency questionnaire and provided fasting blood samples for analysis of glucose and insulin. Insulin resistance was estimated on the basis of fasting glucose and insulin, using the glucose homeostasis model (HOMA scores). Insulin resistance was defined as the upper quartile of the HOMA scores. RESULTS: We found evidence of a U-shaped relationship between alcohol intake and insulin resistance fitted as a continuous variable (HOMA scores) with lowest levels in light drinkers (between 0.5 to 0.99 units per day) relative to the other drinking categories. However no significant association between alcohol intake and HOMA score was observed in fully adjusted analyses, including adjustment for dietary saturated fat and fruit and vegetables intake. In logistic regression analysis with insulin resistance (categorical) as the dependent variable, we observed that ex-drinkers were at higher risk of insulin resistance compared to occasional drinkers independently of age, sex, BMI and waist circumference, (OR=2.4, 95% CI, 1.1-5.7, p=0.04). On further adjustment for potential confounders including diet this association was also attenuated and was non-significant. CONCLUSIONS: The reported effects of alcohol intake on insulin resistance may be confounded by other aspects of lifestyle, especially diet.

An investigation of chemotaxis in the insect parasitic nematode Heterorhabditis bacteriophora.

We tested the chemotactic responses of dauer juvenile stages (DJs) of the insect parasitic nematode Heterorhabditis bacteriophora to a variety of compounds that are known to be highly attractive or highly repellent to Caenorhabditis elegans. While H. bacteriophora DJs respond to alcohols and some aromatic compounds as well as to host metabolites such as uric acid and CO2, the most notable difference in the responses of these two nematodes is that H. bacteriophora DJs are unresponsive to a large number of compounds which C. elegans finds highly attractive. The latter compounds are typical by-products of bacterial metabolism and include aldehydes, esters, ketones and short-chain alcohols. While C. elegans finds long-chain alcohols (e.g. 1-heptanol and 1-octanol) repellent and short-chain alcohols highly attractive, H. bacteriophora DJs are strongly attracted to 1-heptanol, 1-octanol and 1-nonanol and find short-chain alcohols to be only slightly attractive. Parasitic-stage H. bacteriophora nematodes show a very weak chemotactic response to volatile molecules that DJs find highly attractive. Our results suggest that, associated with the adoption of a parasitic mode of life by Heterorhabditis, there was an adaptive change in chemotactic behaviour of the infective stages, resulting in a decreased sensitivity to volatile by-products of bacterial metabolism and an increased sensitivity towards long-chain alcohols and other insect-specific volatiles and possibly also to herbivore-induced plant volatiles.

High-resolution genetic and physical mapping of the cauliflower high-beta-carotene gene Or ( Orange).

Mutation in the cauliflower gene Or causes high levels of beta-carotene to accumulate in various tissues of the plant that are normally devoid of carotenoids. To decipher the molecular basis by which Or regulates carotenoid accumulation, we have undertaken the isolation of Or by a map-based cloning strategy. Two previously isolated, locus-specific, sequence-characterized amplified region (SCAR) markers that flank Or were employed for the analysis of a large segregating population consisting of 1632 F(2) individuals, and a high-resolution genetic linkage map of the Or locus region was developed. To facilitate positional cloning, we constructed a cauliflower genomic library in a bacterial artificial chromosome (BAC) vector, using high molecular weight DNA from Or homozygotes. The BAC library comprises 60,288 clones with an average insert size of 110 kb, and represents an estimated 10-fold coverage of the genome. A BAC contig encompassing the Or locus was established by screening the library with a marker that is closely linked to Or and by identifying overlapping BAC clones by chromosome walking. Physical mapping delimited the Or locus to a 50-kb DNA fragment within a single BAC clone, which corresponds to a genetic interval of 0.3 cM.

Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications.

Acromegaly is an endocrine disorder characterised by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor (IGF)-I, and is associated with malignancy and premature mortality from cardiovascular and respiratory diseases. In particular, there may be an increased risk of colorectal neoplasia, but the exact extent of this is contentious. Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are misleading, but population-based studies on colorectal cancer risk are more consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI: 1.32, 3.14). Possible mechanisms underlying this increased risk include direct actions as a consequence of elevated levels of circulating GH and IGF-I and/or other perturbations within the IGF system. Other possible mechanisms include altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared genetic susceptibility and increased bowel length. However, most explanations only offer indirect evidence, and the expectation of acromegaly as a natural model of colorectal carcinogenesis has not materialised. From a clinical perspective, it seems reasonable to consider a once-only colonoscopic screening at approximately age 55 years, but potential risks and benefits should be balanced.

Coeliac disease and autoimmune Addison's disease: a clinical pitfall.

BACKGROUND: Coeliac disease has an increased prevalence in a number of autoimmune endocrine conditions. An association between coeliac disease and Addison's disease has been proposed in isolated case reports, but has not been formally studied. AIM: To investigate the extent of this association. DESIGN: Prospective screening of patients with confirmed Addison's disease. METHODS: From central computerized records, we identified all living patients with a diagnosis of autoimmune Addison's disease in the past 30 years and presently attending our affiliated hospitals. After exclusions, 44 were invited to attend for screening. RESULTS: Of 41 patients screened, five (12.2%) had coeliac disease: Three were previously diagnosed coeliacs and this was confirmed on review, including examination of biopsy material. A further two had positive IgA-endomysial antibodies. Histological confirmation was obtained in both cases. Neither had laboratory or clinical evidence of malabsorption. DISCUSSION: In this series of patients with Addison's disease, a higher co-morbidity with coeliac disease was observed than in any previously studied endocrine condition. We recommend that coeliac serology (anti-endomysial and tissue transglutaminase antibody) testing be incorporated routinely into the autoimmune screen for other conditions in patients with Addison's disease.