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.

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.

Investigating the Barriers to the Uptake of Diabetic RetinaScreen.

Diabetic retinopathy is a significant complication of diabetes, and the most common cause of blindness in people under the age of 65. The National Diabetic Retinal Screening Programme (Diabetic RetinaScreen) was established to detect sight threatening retinopathies. The purpose of this cross-sectional study is to determine the barriers to the uptake of Diabetic RetinaScreen, to investigate discrepancies in attendance, if any, between patients whose diabetes care is delivered in a large tertiary referral hospital out-patient setting or in general practice, and to evaluate general practitioner's satisfaction with the service. Older age (OR 1.023, 95% CI 1.001 to 1.046) and complications of diabetes, excluding ocular complications, (OR 2.741, 95% CI 1.158 to 6.489) were associated with increased attendance at Diabetic RetinaScreen. Online referral is now available and the preferred method of referral. Efforts to encourage younger patients who do not yet have complications of diabetes may be beneficial.

Scrotal Involvement with Testicular Nonseminomatous Germ Cell Tumour.

A 37-year-old male presented with a traumatic injury to the scrotal region necessitating emergency surgery. Evacuation of a haematoma and bilateral orchidectomy were performed. A left sided nonseminomatous germ cell tumour (NSGCT), predominantly yolk sac, was identified. Microscopic margins were positive for tumour. Initial tumour markers revealed an AFP of 22,854 ng/mL, HCG of <1 mIU/mL, and LDH of 463 IU/L. Eight weeks after surgery, AFP levels remained elevated at 11,646 ng/mL. Computed tomography (CT) scanning demonstrated left inguinal adenopathy, 1.5 cm in max dimension. On review, extensive evidence of scrotal involvement was evident. His tumour was staged as stage IIIC, poor risk NSGCT. He was treated with 4 cycles of bleomycin, etoposide, and cisplatin over a 12-week period. His tumour markers normalised after 3 cycles. There was a marked improvement noted clinically. Follow-up CT scans demonstrated complete resolution of his tumour. He later underwent further surgery to remove a small amount of remaining spermatic cord. Histology revealed no malignant tissue. The patient suffered many complications including testosterone deficiency, osteopenia, infertility, and psychological distress. Discussion. A small proportion of testicular cancer may present in an atypical manner. The scrotum and testicle have markedly different embryonic origins and therefore a distinct anatomic separation. As a result the scrotum is not a typical site of spread of testicular cancer. Case reports have been described that were managed in a similar manner with good outcomes. Therefore, even with significant scrotal involvement, if timely and appropriate treatment is administered, complete resolution of the tumour may be achieved.

Manifestations of Von Hippel Lindau syndrome: a retrospective national review.

INTRODUCTION: Von Hippel Lindau (VHL) disease is a syndrome that is defined by variety of tumours such as cerebellar haemangioblastomas, renal cell carcinomas, phaeochromocytomas, pancreatic adenomas and ear, nose and throat (ENT) adenomas. This disease is often genetic and inherited in an autosomal dominant fashion, and can present in childhood, adolescence or adult life. This study describes the presentation, natural history and manifestations of patients attending our institutions with this condition. We aim to highlight the importance of screening in diagnosing the manifestations of VHL. METHODS: A retrospective review was performed on all patients diagnosed with VHL and coded as such by the national Hospital Inpatient Enquiry Scheme at Beaumont Hospital Dublin and Cork University Hospital. This was performed over a 20 years period between 1989 and 2009. Age, sex, mode of presentation, presence or absence of end stage kidney disease and genotype were documented. Presence or absence of the characteristic tumours of VHL was also recorded, as were the initial presenting features of these tumours. RESULTS: Thirty-six patients were diagnosed with VHL. These patients ranged from 18 to 78 years old. Three patients were members of the Irish travelling community. The most frequent mode of presentation was altered neurological signs (40%), with a significant proportion presenting with haematuria (23%). Patients diagnosed prior to 1995 were more likely to have presented with significant complications of VHL, while those diagnosed after this time were more likely to have been diagnosed via screening. Genetic testing was performed on 17 patients; those who did not have genetic testing performed were more likely to have been diagnosed prior to the era of genetic testing. Thirty-one patients had received screening for complications of VHL including renal cell carcinomas, central nervous system (CNS) haemangioblastomas and phaeochromocytomas. The patients who did not receive any screening presented with neurological symptoms. CONCLUSION: Beaumont Hospital Dublin and Cork University Hospital are tertiary referral centres for nephrology, urology and neurosurgery and deals with a significant proportion of patients diagnosed with VHL in Ireland. This study highlights the significant burden of this illness and emphasizes the importance of screening for these renal/CNS and ENT complications. This study also highlights the importance of family screening in diagnosing this condition.

Prevalence and predictors of influenza and pneumococcal vaccine uptake in patients with diabetes.

The Irish Immunisation Guidelines recommend that people with diabetes mellitus receive the seasonal influenza and pneumococcal vaccines. We aimed to gather data on seasonal influenza vaccine uptake over the previous twelve months, to determine pneumococcal vaccine uptake over a lifetime, and to identify predictors that may influence likelihood of vaccine uptake. A combination of retrospective medical record review and patient questionnaire was undertaken over a three-month period in a diabetes outpatient clinic. Two hundred patients, 28.5% (n=57) with type 1 and 70.5% (n=141) with type 2 diabetes were questioned. Uptake of seasonal influenza vaccine in the previous year was 64.5%. Reported lifetime uptake rate of pneumococcal vaccine was 22%. Increasing age, increasing duration of diabetes and history of recent GP visits significantly increased frequency of influenza vaccination over a five-year period. Significant predictors of influenza vaccination over the previous 12 months included those receiving GP recommendation [OR 10.6 (95% CI 4.3-26.4)] and those aged over 65 [OR 2.8 (1.008-7.8)]. Significant predictors of pneumococcal vaccine uptake included GP recommendation [OR=63 (10-388)] and chronic kidney disease [OR=22 (1.5-312)]. Increased uptake of vaccines is desirable and may be improved by general practices targeting subsets of the population and annual auditing.

Founder effect in the Horn of Africa for an insulin receptor mutation that may impair receptor recycling.

AIMS/HYPOTHESIS: Genetic insulin receptoropathies are a rare cause of severe insulin resistance. We identified the Ile119Met missense mutation in the insulin receptor INSR gene, previously reported in a Yemeni kindred, in four unrelated patients with Somali ancestry. We aimed to investigate a possible genetic founder effect, and to study the mechanism of loss of function of the mutant receptor. METHODS: Biochemical profiling and DNA haplotype analysis of affected patients were performed. Insulin receptor expression in lymphoblastoid cells from a homozygous p.Ile119Met INSR patient, and in cells heterologously expressing the mutant receptor, was examined. Insulin binding, insulin-stimulated receptor autophosphorylation, and cooperativity and pH dependency of insulin dissociation were also assessed. RESULTS: All patients had biochemical profiles pathognomonic of insulin receptoropathy, while haplotype analysis revealed the putative shared region around the INSR mutant to be no larger than 28 kb. An increased insulin proreceptor to ß subunit ratio was seen in patient-derived cells. Steady state insulin binding and insulin-stimulated autophosphorylation of the mutant receptor was normal; however it exhibited decreased insulin dissociation rates with preserved cooperativity, a difference accentuated at low pH. CONCLUSIONS/INTERPRETATION: The p.Ile119Met INSR appears to have arisen around the Horn of Africa, and should be sought first in severely insulin resistant patients with ancestry from this region. Despite collectively compelling genetic, clinical and biochemical evidence for its pathogenicity, loss of function in conventional in vitro assays is subtle, suggesting mildly impaired receptor recycling only.

Severe insulin resistance due to anti-insulin antibodies: response to plasma exchange and immunosuppressive therapy.

Anti-insulin antibodies have been described in two contexts: in insulin-naive individuals (so-called 'insulin autoimmune syndrome') and in patients with insulin-treated diabetes, in whom antibodies are rarely of clinical significance. We report the case of an 68-year-old woman who exhibited a local allergic reaction to subcutaneous insulin followed by severe insulin resistance, evidenced by poor glycaemic control despite treatment with > 3.5 U/kg of insulin per day. She was found to have circulating polyclonal anti-insulin antibodies of the IgG subtype and responded clinically to a course of plasma exchange and immunosuppression with mycophenolate mofetil and, subsequently, intravenous immunoglobulin. Falling titres of antibodies on this regimen correlated with improved glycaemic control. This case suggests that clinicians should be alert to the possibility of insulin resistance due to anti-insulin antibodies and that immunosuppression in this situation may be a valuable therapeutic option.

Weight changes in type 2 diabetes and the impact of gender.

AIMS: Many studies suggest that weight gain occurs during treatment of type 2 diabetes, irrespective of the treatment type. The aim of this study was to address the questions (i) whether weight gain is inevitable in patients treated for type 2 diabetes, and (ii) whether treatment escalation is prompted by a rise in glycaemic control [haemoglobin A 1c (HbA 1c)] or weight gain. METHODS: A diabetes database was used to identify all patients with type 2 diabetes attending our clinic between 1 January 1990 and 31 December 2000. To facilitate further analysis, independent anonymized database resources were established. Data collected included height, weight, gender, HbA(1c), age and diabetes treatment at each visit. RESULTS: One thousand and eighty-four patients were included; after 6 months of treatment, patients' average weight had reduced by 1.0 kg (s.d. 4.6) (p < 0.001). Sixty per cent of the patients had either a decrease or no change in weight, while 40% demonstrated a weight gain. Women demonstrated more weight loss than men. After a mean follow-up of 50 months (s.d. 25.7), 439 patients (40%) who received treatment with diet alone, diet followed by metformin or metformin alone demonstrated a maintained weight reduction in addition to improved glycaemic control. A rise in HbA(1c) rather than weight gain prompted treatment change. CONCLUSIONS: This study provides evidence that weight gain is not a necessary consequence of the treatment of type 2 diabetes. Women were more successful than men in losing weight, and diet, with or without the addition of metformin, was the treatment type most usually associated with weight loss.

Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndrome.

OBJECTIVE/PATIENTS: Rabson-Mendenhall syndrome (RMS) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene. We have identified a pair of siblings with RMS attributable to compound heterozygosity for two insulin receptor mutations, one previously unreported, and have characterized the novel receptor mutation functionally. MEASUREMENTS: Insulin receptor sequencing was performed to identify the mutations. Expression levels of the mature receptor were determined in lymphoblastoid cells from the affected subjects. Further studies of immortalized cell lines transfected with mutant and wild type (WT) receptors were undertaken to characterize the effects of the novel mutation on [(125)I]-labelled insulin binding, proreceptor processing and insulin-stimulated receptor autophosphorylation. RESULTS: Sequencing of the insulin proreceptor coding sequence revealed both siblings to be compound heterozygotes for the missense mutations Arg209His and Gly359Ser in the mature insulin receptor. The former mutation has been described in homozygous form in Donohue syndrome, while the latter is novel. Insulin receptor expression in lymphoblastoid cell lines was present at only 10-30% of that in control cells; studies of immortalized cells transfected with mutant and WT receptors confirmed the reduced expression of the mutant. The degree of impairment of insulin binding and insulin-stimulated receptor autophosphorylation were commensurate with the decrease in expression of the mature receptor. CONCLUSIONS: Loss of function of the novel insulin receptor (INSR) G359S variant is largely accounted for by aberrant proreceptor processing rather than intrinsically impaired signal transduction by the mutant receptor.

Psychiatric co-morbidities in patients attending specialist obesity services in the UK.

BACKGROUND: The prevalence of obesity is rising, but little is known about its psychosocial correlates. AIM: To assess psychological co-morbidities and impairment of quality of life in obese individuals seeking treatment at two specialist centres in the UK. DESIGN: Retrospective analysis of anthropometric and questionnaire data collected at initial clinic visit. METHODS: Patients attending for a first visit between April 2004 and March 2005 completed questionnaires that included scales for measurement of anxiety and depression (Hospital Anxiety and Depression Scale), eating disorder-behaviour (Eating Disorder Inventory 2), assessment of body image (Body Image Assessment for Obesity) and quality of life (Impact of Weight on Quality of Life-Lite). We examined the relationships between variables measured on these scales and anthropometric data. RESULTS: Of 253 questionnaires evaluated, there were elevated scores for depression in 48%, and elevated scores for anxiety in 56%. Twenty-two percent demonstrated scores suggestive of a personality trait that overlaps with an eating disorder; an additional 11.5% had an elevated score for bulimia. About a third of individuals had significant impaired quality of life in the areas of examined. DISCUSSION: Psychological co-morbidities are common in obese individuals attending specialist weight-management clinics, and may merit consideration at (or before) commencement of a weight loss programme.