Liraglutide and the management of overweight and obesity in people with severe mental illness: qualitative sub-study.

BACKGROUND: People with severe mental illness are two to three times more likely to be overweight or have obesity than the general population and this is associated with significant morbidity and premature mortality. Liraglutide 3 mg is a once daily injectable GLP-1 receptor agonist that is licensed for the treatment of obesity in the general population and has the potential to be used in people with severe mental illness. AIMS: To record the expectations and experiences of people with schizophrenia, schizoaffective disorders or first episode psychosis taking daily liraglutide 3 mg injections in a clinical trial for the treatment of obesity. To seek the views of healthcare professionals about the feasibility of delivering the intervention in routine care. METHODS: Qualitative interviews were undertaken with a purposive sub-sample of people with schizophrenia, schizoaffective disorders or first episode psychosis with overweight or obesity who were treated with a daily injection of liraglutide 3 mg in a double-blinded, randomised controlled pilot study evaluating the use of liraglutide for the treatment of obesity. Interviews were also conducted with healthcare professionals. RESULTS: Seventeen patient participants were interviewed. Sixteen took part in the baseline interview, eight completed both baseline and follow-up interviews, and one took part in follow-up interview only. Mean interview duration was thirteen minutes (range 5-37 min). Despite reservations by some participants about the injections before the study, most of those who completed the trial reported no challenges in the timing of or administering the injections. Key themes included despondency regarding prior medication associated weight gain, quality of life impact of weight loss, practical aspects of participation including materials received and clinic attendance. Healthcare professionals reported challenges with recruitment, however, overall it was a positive experience for them and for participants. CONCLUSION: Liraglutide appears to be an acceptable therapy for obesity in this population with limited side effects. The quality of life benefits realised by several intervention participants reinforce the biomedical benefits of achieved weight loss.

The use of liraglutide 3.0 mg daily in the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first episode psychosis: Results of a pilot randomized, double-blind, placebo-controlled trial.

AIM: To investigate the feasibility and acceptability of using liraglutide 3.0 mg daily in the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first episode psychosis. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled pilot trial took place in mental health centres and primary care within Southern Health NHS Foundation Trust. The participants were adults with schizophrenia, schizoaffective or first-episode psychosis prescribed antipsychotic medication who were overweight or obese. The intervention was once-daily subcutaneous liraglutide or placebo, titrated to 3.0 mg daily, for 6 months. The primary outcomes were recruitment, consent, retention and adherence. The secondary exploratory outcomes were weight, HbA1c and Brief Psychiatric Rating Scale. RESULTS: Seven hundred and ninety-nine individuals were screened for eligibility. The most common reasons for exclusion were ineligibility (44%) and inability to make contact (28%). The acceptance rate, as a proportion of all eligible participants, was 12.2%. The most commonly stated reason why eligible candidates declined to participate related to the study-specific medication and protocol (n = 50). Forty-seven participants were randomized, with 79% completing the trial. Participants in the liraglutide arm lost a mean 5.7 ± 7.9 kg compared with no significant weight change in the placebo group (treatment difference -6.0 kg, p = .015). Body mass index, waist circumference and HbA1c were reduced in the intervention group. CONCLUSIONS: This study supports the need for a larger randomized controlled trial to evaluate the use of liraglutide (maximum dose 3.0 mg daily) in the management of obesity in people with severe mental illness.

Mechanisms in endocrinology: Antipsychotic medication and type 2 diabetes and impaired glucose regulation.

OBJECTIVE: There have been concerns about the effects of antipsychotics on weight gain and the development of type 2 diabetes (T2DM). This article aims to provide an up-to-date review on the evidence addressing this issue and the practical implications for the management of people taking antipsychotics in the context of T2DM. METHODS: We carried out searches on MEDLINE/PUBMED and the ClinicalTrials.gov website in August 2017 using the terms 'antipsychotic' and 'diabetes' or 'glucose' citing articles published after 2006 preferentially. RESULTS: Antipsychotics are associated with T2DM and are likely to exert a causal effect of uncertain magnitude. Children and adolescents appear especially vulnerable to these metabolic effects; as T2DM is not common in healthy younger people, the relative risk is more apparent. Antipsychotics act on glucose and insulin homeostasis in a variety of direct and indirect mechanisms. To reduce the increasing health inequalities among individuals with mental illness screening, monitoring and prevention of T2DM is important, as is improved diabetes care in this population. CONCLUSION: It remains unclear whether these antipsychotic medications exacerbate an underlying predisposition to the development of T2DM or have a direct effect. Potential risks need to be weighed up and balanced between improved and lasting mental health benefits and any detrimental physical health side effects. Achieving parity of esteem between mental and physical health is a worldwide priority if we wish to improve life expectancy and quality of life in people with severe mental illness.

Differences in level of confidence in diabetes care between different groups of trainees: the TOPDOC diabetes study.

BACKGROUND: There is an increasing prevalence of diabetes. Doctors in training, irrespective of specialty, will have patients with diabetes under their care. The aim of this further evaluation of the TOPDOC Diabetes Study data was to identify if there was any variation in confidence in managing diabetes depending on the geographical location of trainees and career aspirations. METHODS: An online national survey using a pre-validated questionnaire was administered to trainee doctors. A 4-point confidence rating scale was used to rate confidence in managing aspects of diabetes care and a 6-point scale used to quantify how often trainees would contribute to the management of patients with diabetes. Responses were grouped depending on which UK country trainees were based and their intended career choice. RESULTS: Trainees in Northern Ireland reported being less confident in IGT diagnosis, use of IV insulin and peri-operative management and were less likely to adjust oral treatment, contact specialist, educate lifestyle, and optimise treatment. Trainees in Scotland were less likely to contact a specialist, but more likely to educate on lifestyle, change insulin, and offer follow-up advice. In Northern Ireland, Undergraduate (UG) and Postgraduate (PG) training in diagnosis was felt less adequate, PG training in emergencies less adequate, and reporting of need for further training higher. Trainees in Wales felt UG training to be inadequate. In Scotland more trainees felt UG training in diagnosis and optimising treatment was inadequate. Physicians were more likely to report confidence in managing patients with diabetes and to engage in different aspects of diabetes care. Aspiring physicians were less likely to feel the need for more training in diabetes care; however a clear majority still felt they needed more training in all aspects of care. CONCLUSIONS: Doctors in training have poor confidence levels dealing with diabetes related care issues. Although there is variability between different groups of trainees according to geographical location and career aspirations, this is a UK wide issue. There should be a UK wide standardised approach to improving training for junior doctors in diabetes care with local training guided by specific needs.

Evaluation of a self-administered oral glucose tolerance test.

OBJECTIVE: To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS: Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS: The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS: Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.

One-third of doctors completing specialist training in diabetes fail to secure a substantive consultant post: young Diabetologists' Forum Survey 2010.

Reports have highlighted a shortage of consultant diabetologist posts in the UK. The number of doctors completing specialist training in diabetes has increased in recent years, but little is known about their employment after they receive their certificate of completion of training. An online survey was sent to all doctors who completed specialist diabetes training from January 2008 to September 2010. Of the 95 eligible respondents, 69 (73%) completed the survey (61% men; median age 36 years). Forty-three (62%) respondents secured substantive NHS consultant posts, and of those who gave their job breakdown, 48/51 (94%) were contributing to specialist diabetes care. Five (7%) respondents held substantive academic positions, while 11 (16%) were locum consultants. Seven (9%) respondents worked abroad, with half of these attributing their emigration to lack of opportunities in the UK. When asked about alternative choices, 39% of respondents were likely to seek 'general physician' roles, which equalled the number who would consider emigrating. Overall, only two-thirds of doctors who complete specialist training in diabetes secure substantive NHS consultant positions, which suggests a failure in workforce planning and a lack of expansion of the number of consultant posts despite progression of the diabetes epidemic.

Protocol for a national audit on self-reported confidence levels, training requirements and current practice among trainee doctors in the UK: the Trainees Own Perception of Delivery of Care in Diabetes (TOPDOC) Study.

BACKGROUND: As the incidence and prevalence of diabetes increases across the world, resource pressures require doctors without specialist training to provide care for people with diabetes. In the UK, national standards have been set to ensure quality diabetes care from diagnosis to the management of complications. In a multi-centre pilot study, we have demonstrated a lack of confidence among UK trainee doctors in managing diabetes. Suboptimal confidence was identified in a number of areas, including the management of diabetes emergencies. A national survey would clarify whether the results of our pilot study are representative and reproducible. METHODS/DESIGN: Target cohort: All postgraduate trainee doctors in the UK. DOMAINS STUDIED: The self reported online survey questionnaire has 5 domains: (1) confidence levels in the diagnosis and management of diabetes, (2) working with diabetes specialists, (3) perceived adequacy of training in diabetes (4) current practice in optimising glycaemic control and (5) perceived barriers to seeking euglycaemia.Assessment tools: Self-reported confidence is assessed using the 'Confidence Rating' (CR) scale for trainee doctors developed by the Royal College of Physicians. This scale has four points--('not confident' (CR1), 'satisfactory but lacking confidence' (CR2), 'confident in some cases (CR3) and 'fully confident in most cases' (CR4).Frequency of aspects of day-to-day practice is assessed using a six-point scale. Respondents have a choice of 'always' (100%), 'almost always' (80-99%), 'often' (50-79%), 'not very often' (20-49%) and 'rarely' (5-19%) or never (less than 5%). DISCUSSION: It is anticipated that the results of this national study will clarify confidence levels and current practice among trainee doctors in the provision of care for people with diabetes. The responses will inform efforts to enhance postgraduate training in diabetes, potentially improving the quality of care for people with diabetes.

Life expectancy in individuals with type 2 diabetes: implications for annuities.

BACKGROUND: Insurance companies often offer people with diabetes ''enhanced impaired life annuity'' at preferential rates, in view of their reduced life expectancy. OBJECTIVE: To assess the appropriateness of ''enhanced impaired life annuity'' rates for individuals with type 2 diabetes. Patients. There were 4026 subjects with established type 2 diabetes (but not known cardiovascular or other life-threatening diseases) enrolled into the UK Lipids in Diabetes Study. Measurements. Estimated individual life expectancy using the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. RESULTS: Subjects were a mean (SD) age of 60.7 (8.6) years, had a blood pressure of 141/83 (17/10) mm Hg, total cholesterol level of 4.5 (0.75) mmol/L, HDL cholesterol level of 1.2 (0.29) mmol/L, with median (interquartile range [IQR]) known diabetes duration of 6 (3-11) years, and HbA(1c) of 8.0% (7.2-9.0). Sixty-five percent were male, 91% white, 4% Afro-Caribbean, 5% Indian-Asian, and 15% current smokers. The UKPDS Outcomes Model median (IQR) estimated age at death was 76.6 (73.8-79.5) years compared with 81.6 (79.4-83.2) years, estimated using the UK Government Actuary's Department data for a general population of the same age and gender structure. The median (IQR) difference was 4.3 (2.8-6.1) years, a remaining life expectancy reduction of almost one quarter. The highest value annuity identified, which commences payments immediately for a 60-year-old man with insulin-treated type 2 diabetes investing 100,000, did not reflect this difference, offering 7.4K per year compared with 7.0K per year if not diabetic. CONCLUSIONS: The UK Government Actuary's Department data overestimate likely age at death in individuals with type 2 diabetes, and at present, ''enhanced impaired life annuity'' rates do not provide equity for people with type 2 diabetes. Using a diabetes-specific model to estimate life expectancy could provide valuable information to the annuity industry and permit more equitable annuity rates for those with type 2 diabetes.

Perceptions of heart attack risk amongst individuals with diabetes.

AIM: Individuals with diabetes are at increased risk of cardiovascular disease (CVD). There is good evidence that this risk can be reduced by pharmacotherapies and lifestyle modification. Despite this, knowledge of CVD risk amongst individuals with diabetes remains poor. We undertook a qualitative study to investigate lay perceptions of heart attack risk amongst individuals with diabetes in order to gather information about underlying perceptions concerning risk and risk reduction strategies. METHODS: We conducted three focus groups in Oxford using an open-ended question map. Content analysis was performed to identify recurring themes, similar patterns, distinctions and supportive quotations. RESULTS: Concern about having a heart attack varied widely. A commonly held view was that a 10-year heart attack risk of 10% or greater was high and being aware of one's risk was important so that lifestyle changes or other interventions could be implemented. Participants consistently viewed physical activity as potentially harmful. Almost all participants sought healthcare and lifestyle advice from their primary healthcare providers in the first instance, preferring this to information in the lay press or government campaigns. CONCLUSION: The focus groups have allowed us to better understand lay perceptions of, and underlying assumptions about, CVD risk. These findings may be of use when discussing CVD risk and risk reduction strategies in primary care.

Use of focus groups to develop methods to communicate cardiovascular disease risk and potential for risk reduction to people with type 2 diabetes.

BACKGROUND: People need to perceive a risk in order to build an intention-to-change behaviour yet our ability to interpret information about risk is highly variable. OBJECTIVES: We aimed to use a user-centred design process to develop an animated interface for the UK Prospective Diabetes Study (UKPDS) Risk Engine to illustrate cardiovascular disease (CVD) risk and the potential to reduce this risk. In addition, we sought to use the same approach to develop a brief lifestyle advice intervention. METHODS: Three focus groups were held. Participants were provided with examples of materials used to communicate CVD risk and a leaflet containing a draft brief lifestyle advice intervention and considered their potential to increase motivation-to-change behaviours including diet, physical activity, and smoking in order to reduce CVD risk. Discussions were tape-recorded, transcribed and coded and recurring themes sought. RESULTS: Sixty-two percent of participants were male, mean age was 66 years (range = 47-76 years) and median age at leaving full-time education was 18 years (range = 15-40 years). Sixteen had type 2 diabetes and none had a prior history of CVD. Recurring themes from focus group discussions included the following: being less numerate is common, CVD risk reduction is important and a clear visual representation aids comprehension. CONCLUSION: A simple animated interface of the UKPDS Risk Engine to illustrate CVD risk and the potential for reducing this risk has been developed for use as a motivational tool, along with a brief lifestyle advice intervention. Future work will investigate whether use of this interactive version of the UKPDS Risk Engine and brief lifestyle advice is associated with increased behavioural intentions and changes in health behaviours designed to reduce CVD risk.

The upper limit of the reference range for thyroid-stimulating hormone should not be confused with a cut-off to define subclinical hypothyroidism.

The upper limit of the reference range for serum thyroid-stimulating hormone (TSH) is used to assist in identifying individuals with hypothyroidism. Improvements in TSH assays have led to better definition of the lower limit of the reference range, but the upper limit of the range for a healthy population is currently a topic of some debate. Population studies have improved our understanding of the clinical implications of elevated serum TSH concentrations in terms of future progression to hypothyroidism, but have not yet fully elucidated the correlation of modestly elevated TSH levels with long-term morbidity. This paper will review the current debate including the arguments for and against reducing the upper limit of the TSH range, whether such a level should be based on evidence from epidemiological studies, and the implications of categorizing large numbers of people with subclinical hypothyroidism. The impact of using different methodologies for the measurement of TSH and the inherent variability of results on reference ranges is also discussed. We argue that the reference range for TSH should be assay-specific and be determined by standard techniques in normal populations as recommended by the National Academy of Clinical Biochemistry. In contrast, we suggest that a decision level be determined separately from epidemiological studies to identify a population with subclinical hypothyroidism. Serial monitoring of TSH in this population deserves further study as a means of identifying those at risk of progressing to frank hypothyroidism and meriting treatment.

Primary prevention of cardiovascular events in diabetes: is there a role for aspirin?

The POPADAD (Prevention Of Progression of Arterial Disease And Diabetes) study did not show a benefit for low-dose aspirin therapy or administration of antioxidants for the primary prevention of cardiovascular disease events in individuals with diabetes and asymptomatic peripheral arterial disease. Although low-dose aspirin continues to be recommended in international guidelines, no convincing trial-based evidence exists that supports its routine use for primary prevention of cardiovascular disease in people with diabetes. This paradox is unhelpful and the guidelines should be relaxed until definitive evidence becomes available.

Performance of the UK Prospective Diabetes Study Risk Engine and the Framingham Risk Equations in Estimating Cardiovascular Disease in the EPIC- Norfolk Cohort.

OBJECTIVE: The purpose of this study was to examine the performance of the UK Prospective Diabetes Study (UKPDS) Risk Engine (version 3) and the Framingham risk equations (2008) in estimating cardiovascular disease (CVD) incidence in three populations: 1) individuals with known diabetes; 2) individuals with nondiabetic hyperglycemia, defined as A1C >or=6.0%; and 3) individuals with normoglycemia defined as A1C <6.0%. RESEARCH DESIGN AND METHODS: This was a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40-79 years recruited from U.K. general practices attended a health examination (1993-1998) and were followed for CVD events/death until April 2007. CVD risk estimates were calculated for 10,137 individuals. RESULTS: Over 10.1 years, there were 69 CVD events in the diabetes group (25.4%), 160 in the hyperglycemia group (17.7%), and 732 in the normoglycemia group (8.2%). Estimated CVD 10-year risk in the diabetes group was 33 and 37% using the UKPDS and Framingham equations, respectively. In the hyperglycemia group, estimated CVD risks were 31 and 22%, respectively, and for the normoglycemia group risks were 20 and 14%, respectively. There were no significant differences in the ability of the risk equations to discriminate between individuals at different risk of CVD events in each subgroup; both equations overestimated CVD risk. The Framingham equations performed better in the hyperglycemia and normoglycemia groups as they did not overestimate risk as much as the UKPDS Risk Engine, and they classified more participants correctly. CONCLUSIONS: Both the UKPDS Risk Engine and Framingham risk equations were moderately effective at ranking individuals and are therefore suitable for resource prioritization. However, both overestimated true risk, which is important when one is using scores to communicate prognostic information to individuals.

Myopathy following postoperative ablative radioiodine for follicular carcinoma of the thyroid.

We highlight a case of disabling myopathy following radioablative iodine treatment for follicular carcinoma of the thyroid. A 34-year-old man presented with a tender neck swelling, ultrasound and biopsy were suggestive of thyroid malignancy. Thyroidectomy was undertaken and histology confirmed follicular carcinoma of the thyroid. Treatment with ablative radioiodine followed and within days the patient developed disabling myopathy. Investigations to date do not reveal any other cause for the myopathy and there is no evidence to suggest that this is a paraneoplastic phenomenon. We believe this is the first reported case of ablative radioiodine-induced mypoathy.

The impact of individualised cardiovascular disease (CVD) risk estimates and lifestyle advice on physical activity in individuals at high risk of CVD: a pilot 2 x 2 factorial understanding risk trial.

BACKGROUND: There is currently much interest in encouraging individuals to increase physical activity in order to reduce CVD risk. This study has been designed to determine if personalised CVD risk appreciation can increase physical activity in adults at high risk of CVD. METHODS/DESIGN: In a 2 x 2 factorial design participants are allocated at random to a personalised 10-year CVD risk estimate or numerical CVD risk factor values (systolic blood pressure, LDL cholesterol and fasting glucose) and, simultaneously, to receive a brief lifestyle advice intervention targeting physical activity, diet and smoking cessation or not. We aim to recruit 200 participants from Oxfordshire primary care practices. Eligibility criteria include adults age 40-70 years, estimated 10-year CVD risk > or =20%, ability to read and write English, no known CVD and no physical disability or other condition reducing the ability to walk. Primary outcome is physical activity measured by ActiGraph accelerometer with biochemical, anthropometrical and psychological measures as additional outcomes. Primary analysis is between group physical activity differences at one month powered to detect a difference of 30,000 total counts per day of physical activity between the groups. Additional analyses will seek to further elucidate the relationship between the provision of risk information, and intention to change behaviour and to determine the impact of both interventions on clinical and anthropometrical measures including fasting and 2 hour plasma glucose, fructosamine, serum cotinine, plasma vitamin C, body fat percentage and blood pressure. DISCUSSION: This is a pilot trial seeking to demonstrate in a real world setting, proof of principal that provision of personalised risk information can contribute to behaviour changes aimed at reducing CVD risk. This study will increase our understanding of the links between the provision of risk information and behaviour change and if successful, could be used in clinical practice with little or no modification.