Diarmuid Smith

The natural history of surgically treated but radiotherapy‐naïve nonfunctioning pituitary adenomas

Background and objectives  Transsphenoidal surgery is indicated for patients with nonfunctioning pituitary adenomas (NFPAs) causing compressive symptoms. Previous studies attempting to define the rate of recurrence/regrowth of surgically treated but radiation‐naïve NFPAs were somewhat limited by selection bias and/or small numbers and/or lack of consistency of findings between studies. A better understanding of the natural history of this condition could allow stratification of recurrence risk and inform future management. We aimed to define the natural history of a large, mainly unselected cohort with surgically treated, radiotherapy (RT)‐naïve NFPAs and to try to identify predictors of recurrence/regrowth.

Morbidity and mortality in patients with craniopharyngioma after surgery.

Objective  Craniopharyngioma (CP) is a benign tumour of the suprasellar region that is associated with increased morbidity and mortality in comparison with other causes of hypopituitarism. We aimed to establish the rate and causes of mortality and morbidity in patients with CP who attended our centre.

Clinical insights into adipsic diabetes insipidus: a large case series.

Objective  Adipsic diabetes insipidus (DI) causes significant hypernatraemia. Morbidity and mortality data for patients with adipsic DI have been previously published as single case reports, rather than as formal trials or case series from units with established management protocols. Our objective was to describe morbidity and mortality in patients with adipsic DI attending a tertiary referral centre, representing the largest reported series of adipsic DI, and to suggest management protocols for such patients, based on our extensive experience of this condition.

Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma

objective  In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed.

Similar to adiponectin, serum levels of osteoprotegerin are associated with obesity in healthy subjects

An increase in serum osteoprotegerin (OPG) is associated with type 2 diabetes mellitus, the severity of vascular calcification, and coronary artery disease. Obesity is a risk factor for diabetes and cardiovascular disease, but little is known about the relationship between OPG and obesity. The purpose of this study was to determine if changes in body mass index (BMI) and insulin sensitivity influence circulating OPG in healthy subjects. A total of 100 subjects (36 lean, 41 overweight, and 23 obese) with normal glucose tolerance, blood pressure, and electrocardiogram stress test result volunteered for this study. Insulin sensitivity was estimated using a 2-hour oral glucose tolerance test with oral glucose insulin sensitivity analysis. Osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),soluble receptor activator of nuclear factor-κβ ligand (sRANKL), and adiponectin were analyzed using commercially available enzyme-linked immunosorbent assays. Osteoprotegerin (P < .01) and adiponectin (P < .001) were significantly decreased in the obese compared with lean subjects. There was no significant difference between BMI categories for TRAIL or sRANKL. Controlling for age and sex, there was a significant correlation between OPG and adiponectin (r = 0.391, P < .001), BMI (r = -0.331, P < .001), waist circumference (r = -0.268, P < .01), homeostasis model assessment of insulin resistance (r = -0.222, P < .05), and oral glucose insulin sensitivity (r = 0.221, P < .05). Both OPG and adiponectin were negatively correlated with body weight, BMI, waist circumference, and fasting plasma insulin while being positively correlated with insulin sensitivity (P < .05). Controlling for age, sex, and BMI, TRAIL was positively related to fat mass (r = 0.373, P < .001) and waist circumference (r = 0.257, P < .05). In contrast to patients with type 2 diabetes mellitus, circulating OPG is lower in obese, but otherwise healthy subjects and is positively correlated with indices of insulin sensitivity.

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

BackgroundDiabetes 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.MethodsSemi-structured interviews with 35 individuals with Type 1 diabetes (23–30 years of age).ResultsThis 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.ConclusionsSome 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.

Vascular calcification in type-2 diabetes and cardiovascular disease: Integrative roles for OPG, RANKL and TRAIL

Vascular calcification (VC), a disorder that causes blood vessel hardening and dysfunction, is a significant risk factor for type-2 diabetes mellitus (T2DM), which invariably manifests associated cardiovascular complications. Although the clinical effects of VC have been well-documented, the precise cellular events underlying the manifestation and progression of VC are only now coming to light. Current research models indicate that VC likely involves signalling pathways traditionally associated with bone remodelling, such as the OPG/RANKL/TRAIL signalling system. In this respect, receptor activator of NF-κB ligand (RANKL) promotes VC whilst osteoprotegerin (OPG) acts as a RANKL decoy receptor to block this effect, events that contrast with the known functional influence of these proteins during bone metabolism. Moreover, evidence suggests that tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), an alternative decoy ligand for OPG, may exert an anti-calcific influence within the vasculature. In the current review, we conduct a timely examination of this complex VC pathology from both mechanistic and therapeutic perspectives. Our objectives are twofold: (i) to critically assess our current understanding of both osteogenic and vascular calcification pathways, with particular focus on the co-interactive roles of OPG, RANKL, and TRAIL. Extensive in vitro, in vivo, and clinical studies will therefore be reviewed and critical findings highlighted; and (ii) to examine a range of therapeutic approaches of potential relevance to VC pathology. In this regard, a clear focus on VC as it applies to T2DM and cardiovascular disease (and particularly atherosclerosis) will be maintained.

Osteoprotegerin and biomarkers of vascular inflammation in type 2 diabetes

Osteoprotegerin (OPG), receptor activator for nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor–related apoptosis‐inducing ligand (TRAIL) are newly discovered members of the tumour necrosis factor‐alpha receptor superfamily. While their role in bone metabolism is well described, their function within the vasculature is poorly understood. OPG inhibits vascular calcification in vitro and high serum levels have been demonstrated in type 2 diabetes, but serum RANKL and TRAIL and their potential correlation with well‐established biomarkers of subclinical vascular inflammation such as high‐sensitivity C‐reactive protein (hsCRP) and interleukin‐6 (IL‐6) have not been described.

Central pontine myelinolysis complicating treatment of the hyperglycaemic hyperosmolar state

Abstract Central pontine myelinolysis (CPM) is well recognized to occur in a variety of clinical settings, but particularly following rapid correction of severe hyponatraemia. The development of CPM as a result of rapid shifts in plasma osmolality during the treatment of the hyperglycaemic hyperosmolar state (HHS) has hitherto been described in only one case. We report a second case in which this complication occurred in association with treatment of the HHS. The patient was a 49-year-old woman who presented to another hospital with drowsiness and a plasma glucose of 106 mmol/L. Her admission plasma sodium was 135 mmol/L. She received treatment with intravenous insulin and 0.9% normal saline, and there was a rapid drop in plasma glucose by 60 mmol/L within 6 h, which was associated with a rebound rise of plasma sodium to 159 mmol/L. Her plasma glucose and sodium were later stabilized. When the patient was transferred to our hospital a few days later, she was noted to have flaccid quadraparesis and pseudobulbar palsy. A magnetic resonance imaging scan revealed a pontine lesion consistent with CPM. She made a gradual recovery over several months with intensive rehabilitation and eventually returned to near normal functional capacity. This is the second case report in the literature of CPM complicating the management of HHS and highlights the importance of the judicious and measured correction of hyperglycaemia and the appropriate management of fluid replacement and electrolyte balance when treating this condition.

The Irish DAFNE Study Protocol: A cluster randomised trial of group versus individual follow-up after structured education for Type 1 diabetes

BackgroundStructured education programmes for individuals with Type 1 diabetes have become a recognised means of delivering the knowledge and skills necessary for optimal self-management of the condition. The Dose Adjustment for Normal Eating (DAFNE) programme has been shown to improve biomedical (HbA1c and rates of severe hypoglycaemia) and psychosocial outcomes for up to 12 months following course delivery. The optimal way to support DAFNE graduates and maintain the benefits of the programme has not been established. We aimed to compare 2 different methods of follow-up of DAFNE graduates in a pragmatic clinical trial delivered in busy diabetes clinics on the island of Ireland.MethodsSix participating centres were cluster randomised to deliver either group follow-up or a return to traditional one-to-one clinic visits. In the intervention arm group follow-up was delivered at 6 and 12 months post DAFNE training according to a curriculum developed for the study. In the control arm patients were seen individually in diabetes clinics as part of routine care. Study outcomes included HbA1c levels, self-reported rates of severe hypoglycaemia, body weight and measures of diabetes wellbeing and quality of life. These were measured at 6, 12 and 18 months after recruitment. Generalisability (external validity) was maximised by recruiting study participants from existing DAFNE waiting lists in each centre, by using broad inclusion criteria (including HbA1c values less than 13 percent with no lower limit) and by using existing clinic staff to deliver the training and follow-up. Internal validity and treatment fidelity were maximised by quality assuring the training of all DAFNE educators, by external peer review of the group follow-up sessions and by striving for full attendance at follow-up visits. Assays of HbA1c were undertaken in a central laboratory.DiscussionThis pragmatic clinical trial evaluating group follow-up after a structured education programme has been designed to have broad generalisability. The results should inform how best to manage the well educated patient with Type 1 diabetes in the real world of clinical practiceTrial registrationCurrent Controlled Trials ISRCTN79759174