Foot ulceration and its association with mortality in diabetes mellitus: a meta-analysis.

BACKGROUND: Diabetic foot ulcers portend an almost twofold increase in all-cause mortality compared with diabetes on its own. AIM: To investigate the association between diabetic foot ulcers and risk of death. METHODS: We performed a meta-analysis of all observational studies investigating the association between diabetic foot ulcers and all-cause mortality. Risk ratios and risk differences were pooled in a random-effects model. The I2 statistic was used to quantify heterogeneity between studies. RESULTS: Altogether, we identified 11 studies that reported 84 131 deaths from any cause in 446 916 participants with diabetes during a total of 643 499 person-years of follow-up. The crude event rate for all-cause mortality in individuals with diabetes who did not develop foot ulceration was 22% lower at 181.5 deaths (per 1000 person-years) than in those who developed foot ulcers (230.8 per 1000 person-years). Diabetic foot ulceration was associated with an increased risk of all-cause mortality (pooled relative risk 2.45, 95% CI 1.85-2.85). We did not observe any tangible differences in risk of all-cause mortality from diagnosis in studies reporting a mean duration of follow-up of ≤3 years (relative risk 2.43, 95% CI 2.27-2.61) or >3 years (relative risk 2.26, 95% CI 2.13-2.40) years. Funnel plot inspection revealed no significant publication bias among studies included in this meta-analysis. CONCLUSIONS: Our study shows an excess rate of all-cause mortality in people with diabetic foot ulceration when compared to those without foot ulceration. It is imperative that early interventions to prevent foot ulceration and modify cardiovascular disease risk factors are put in place to reduce excess mortality.

Links between the amount of antipsychotic medication prescribed per population at general practice level, local demographic factors and medication selection.

BACKGROUND: Antipsychotic medications are the first-line pharmacological intervention for severe mental illnesses (SMI) such as schizophrenia and other psychoses, while also being used to relieve distress and treat neuropsychiatric symptoms in dementia. Our aim was to examine the factors relating to antipsychotic prescribing in general practices across England and how cost changes in recent years have impacted on antipsychotic prescribing. METHODS: The study examined over time the prescribing volume and prices paid for antipsychotic medication by agent in primary care. Monthly prescribing in primary care was consolidated over 5 years (2013-2018) and DDD amount from WHO/ATC for each agent was used to convert the amount to total DDD/practice. The defined Daily Dose (DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. RESULTS: We included 5750 general practices with practice population > 3000 and with > 30 people on their SMI register. In 2018/19 there were 10,360,865 prescriptions containing 136 million DDD with costs of £110 million at an average cost of £0.81/DDD issued in primary care. In 2017/18 there was a sharp increase in overall prices and they had not reduced to expected levels by the end of the 2018/19 evaluation year. There was a gradual increase in antipsychotic prescribing over 2013-2019 which was not perturbed by the increase in drug price in 2017/18. The strongest positive relation to increased prescribing of antipsychotics came from higher social disadvantage, higher population density (urban), and comorbidities e.g. chronic obstructive pulmonary disease (COPD). Higher % younger and % older populations, northerliness and non-white (Black and Minority Ethnic(BAME)) ethnicity were all independently associated with less antipsychotic prescribing. Higher DDD/general practice population was linked with higher proportion(%) injectable, higher %liquid, higher doses/prescription and higher %zuclopenthixol depot. Less DDD/population was linked with general practices using higher % risperidone and higher spending/dose of antipsychotic. CONCLUSIONS: The levels of antipsychotic prescribing at general practice level are driven by social factors/comorbidities. We found a link between depot prescriptions with higher antipsychotic DDD and risperidone prescriptions with lower antipsychotic DDD. It is important that all prescribers are aware of these drivers / links.

Developing a foot ulcer risk model: what is needed to do this in a real-world primary care setting?

AIM: To determine how routinely collected data can inform a risk model to predict de novo foot ulcer presentation in the primary care setting. METHODS: Data were available on 15 727 individuals without foot ulcers and 1125 individuals with new foot ulcers over a 12-year follow-up in UK primary care. We examined known risk factors and added putative risk factors in our logistic model. RESULTS: People with foot ulcers were 4.2 years older (95% CI 3.1-5.2) than those without, and had higher HbA1c % (mean 7.9 ± 1.9 vs 7.5 ± 1.7) / HbA1c mmol/mol (63 ± 21 vs 59 ± 19) (p<0.0001) concentration [+0.45 (95% CI 0.33-0.56), creatinine level [+6.9 µmol/L (95% CI 4.1-9.8)] and Townsend score [+0.055 (95% CI 0.033-0.077)]. Absence of monofilament sensation was more common in people with foot ulcers (28% vs 21%; P<0.0001), as was absence of foot pulses (6.4% vs 4.8%; P=0.017). There was no difference between people with or without foot ulcers in smoking status, gender, history of stroke or foot deformity, although foot deformity was extremely rare (0.4% in people with foot ulcers, 0.6% in people without foot ulcers). Combining risk factors in a single logistic regression model gave modest predictive power, with an area under the receiver-operating characteristic curve of 0.65 (95% CI 0.62-0.67). The prevalence of ulceration in the bottom decile of risk was 1.8% and in the top decile it was 13.4% (compared with an overall prevalence of 6.5%); thus, the presence of all six risk factors gave a relative risk of 7.4 for development of a foot ulcer over 12 years. CONCLUSION: We have made some progress towards defining a variable set that can be used to create a foot ulcer prediction model. More accurate determination of foot deformity/pedal circulation in primary care may improve the predictive value of such a future risk model, as will identification of additional risk variables.

Route to improving Type 1 diabetes mellitus glycaemic outcomes: real-world evidence taken from the National Diabetes Audit.

AIM: To use general practice-level data for England, available through the National Diabetes Audit, and primary care prescribing data to identify prescription treatment factors associated with variations in achieved glucose control (HbA1c ). METHODS: General practice-level National Diabetes Audit data on Type 1 diabetes, including details of population characteristics, services, proportion of people achieving target glycaemic control [HbA1c ≤58 mmol/mol (7.5%)] and proportion of people at high glycaemic risk [HbA1c >86 mmol/ml (10%)], were linked to 2013-2016 primary care diabetes prescribing data on insulin types and blood glucose monitoring for all people with diabetes. RESULTS: A wide variation was found between the 10th percentile and the 90th percentile of general practices in both target glycaemic control (15.6% to 44.8%, respectively) and high glycaemic risk (4.8% to 28.6%, respectively). Our analysis suggests that, given the extrapolated total of 280 000 people with Type 1 diabetes in the UK, there may be the potential to increase the number of those within target glycaemic control from 80 000 to 101 000; 53% of this increase (11 000 people) would result from service improvements and 47% (10 000 people) from medication and technology changes. The same improvements would also provide the opportunity to reduce the number of people at high glycaemic risk from 42 000 to 26 500. A key factor associated with practice-level target HbA1c achievement would be greater use of insulin pumps for up to an additional 56 000 people. CONCLUSION: If the HbA1c achievement rates in service provision, medication and use of technology currently seen in practices in the 90th percentile were to be matched with regard to HbA1c achievement rates in all general practices, glycaemic control might be improved for 36 500 people, with all the attendant health benefits.

Higher levels of apomorphine and rotigotine prescribing reduce overall secondary healthcare costs in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) affects around 100,000 people in England. A number of non-oral therapies can improve both the quality of life and reduce patient needs for health and social care. However, these can be relatively expensive at £2000-£10,000 per year per patient. Our aim was to examine how prescribing of these agents relates to secondary care costs. METHODS: Using practice level primary care prescribing data and hospital episode statistical data in England, we investigated the relation between general practitioner prescriptions of apomorphine injections/rotigotine patches and the secondary care costs accrued for their diagnosed PD patients for 2011-2014. The median age of the PD patients was 78 years. RESULTS: In the period 2011-2014, 58% of the average annual £437 million secondary care costs for PD patients came from non-elective admissions. 80% of this came from seven Healthcare Resource Group Chapters linked to PD comorbidities. Compared with practices not using non-oral therapies, practices prescribing Apomorphine saved £897 per year per patient of secondary care costs to offset the average additional prescribing cost of £475 per overall patient per year. For Rotigotine, saving was £718 per year per patient of secondary care costs offsetting £137 prescribing cost. Practices in the highest quartile of non-oral prescribing were using non-oral agents in up to 28% of their PD patients. CONCLUSIONS: Those practices which used more non-oral therapies appear to incur less secondary care costs. A total of 70% of the advanced PD patients are not being given access to non-oral treatment. This is a challenge for all physicians looking after the older patient.

Serum testosterone, testosterone replacement therapy and all-cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins.

BACKGROUND: Low testosterone levels occur in over 40% of men with type 2 diabetes mellitus (T2DM) and have been associated with increased mortality. Testosterone replacement together with statins and phosphodiesterase 5 inhibitors (PDE5I) are widely used in men with T2DM. PURPOSE: To determine the impact of testosterone and testosterone replacement therapy (TRT) on mortality and assess the independence of this effect by adjusting statistical models for statin and PDE5I use. METHODS: We studied 857 men with T2DM screened from five primary care practices during April 2007-April 2009. Of the 857 men, 175/637 men with serum total testosterone ≤ 12 nmol/l or free testosterone (FT) ≤ 0.25 nmol/l received TU for a mean of 3.8 ± 1.2 (SD) years. PDE5I and statins were prescribed to 175/857 and 662/857 men respectively. All-cause mortality was the primary end-point. Cox regression models were used to compare survival in the three testosterone level/treatment groups, the analysis adjusted for age, statin and PDE5I use, BMI, blood pressure and lipids. RESULTS: Compared with the Low T/untreated group, mortality in the Normal T/untreated (HR: 0.62, CI: 0.41-0.94) or Low T/treated (HR: 0.38, CI: 0.16-0.90) groups was significantly reduced. PDE5I use was significantly associated with reduced mortality (HR: 0.21, CI: 0.066-0.68). After repeating the Cox regression in the 682 men not given a PDE5I, mortality in the Normal T/untreated and Low T/treated groups was significantly lower than that in the reference Low T/untreated group. Mortality in the PDE5I/treated was significantly reduced compared with the PDE5I/untreated group (OR: 0.06, CI: 0.009-0.47). CONCLUSIONS: Testosterone replacement therapy is independently associated with reduced mortality in men with T2DM. PDE5I use, included as a confounding factor, was associated with decreased mortality in all patients and, those not on TRT, suggesting independence of effect. The impact of PDE5I treatment on mortality (both HR and OR < 0.25) needs confirmation by independent studies.

Measuring vitamin D levels: surrogates are insufficient.

AIMS: With the increasing evidence of adverse consequences because of low vitamin D levels on health demand for vitamin D, screening is increasing. The objective of the study was to assess whether parathyroid hormone (PTH) levels/bone profile is sufficient to identify patients with vitamin D insufficiency or deficiency, or whether vitamin D should be measured directly. METHODOLOGY: A total of 1560 serum specimens, with requests for 25-hydroxyvitamin D (25-OH vitamin D), calcium, phosphate, alkaline phosphatase (ALP), creatinine and PTH on the same sample were analysed at Salford Royal Hospital from November 2010 to November 2012. RESULTS: The prevalence of total vitamin D insufficiency or deficiency (defined as total 25-OH vitamin D < 50 nmol/l) was 62.9% (981/1560) overall, with males having higher proportions (67.2 vs. 59.3 per cent; χ(2) = 8.78, p = 0.003). There was no overall trend in mean serum adjusted calcium across categories of 25-OH vitamin D status but mean serum phosphate was significantly lower (F = 6.53, p < 0.0001) in patients with a 25-OH vitamin D level < 50 nmol/l. However in patients with vitamin D deficiency, a significant proportion had PTH, calcium, phosphate and alkaline phosphatase levels within the laboratory normal range. Even at a 25-OH vitamin D < 10 nmol/l, 71.6% had a normal PTH, 89.8% had normal serum calcium levels, 84.9% had normal phosphate levels and 81.6% had normal serum ALP. CONCLUSIONS: Therefore, despite the costs associated with the measurement of vitamin D, our findings show that no surrogate is adequate for screening for vitamin D deficiency.

Sex differences in plasma clozapine and norclozapine concentrations in clinical practice and in relation to body mass index and plasma glucose concentrations: a retrospective survey.

BACKGROUND: Clozapine is widely prescribed and, although effective, can cause weight gain and dysglycemia. The dysmetabolic effects of clozapine are thought to be more prevalent in women with this gender on average attaining 17 % higher plasma clozapine concentrations than men. METHODS: We investigated the relationship between dose, body mass index (BMI), plasma glucose concentration, and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in 100 individuals with a severe enduring mental illness. RESULTS: Mean (10th/90th percentile) plasma clozapine concentrations were higher for women [0.49 (0.27-0.79) mg/L] compared with men [0.44 (0.26-0.70) mg/L] (F = 2.2; p = 0.035). There was no significant gender difference in the prescribed clozapine dose. BMI was significantly higher in women [mean (95 % CI) = 34.5 (26.0-45.3)] for females compared with 32.5 (25.2-41.0) for males. Overall, BMI increased by 0.7 kg/m(2) over a mean follow-up period of 210 days. A lower proportion, 41 % of women had a fasting blood glucose ≤6.0 mmol/L (<6.0 mmol/L is defined by the International Diabetes Federation as normal glucose handling), compared with 88 % of men (χ (2) = 18.6, p < 0.0001). CONCLUSIONS: We have shown that mean BMI and blood glucose concentrations are higher in women prescribed clozapine than in men. Women also tended to attain higher plasma clozapine concentrations than men. The higher BMI and blood glucose in women may relate to higher tissue exposure to clozapine, as a consequence of sex differences in drug metabolism.

No role for tri-iodothyronine (T3) testing in the assessment of levothyroxine (T4) over-replacement in hypothyroid patients.

Tri-iodothyronine (T3) is a sensitive marker of endogenous hyperthyroidism. In levothyroxine (T4)-induced hyperthyroidism, there is no reason for T3 to be elevated, but this test is often requested in over-treated hypothyroid patients. This study investigated how informative T3 levels are in these patients. Our hypothesis is that T3 measurement would not add anything to the assessment of T4 over-replacement in primary hypothyroidism. Over a 15-week period, consecutive thyroid function test requests in patients on levothyroxine had T3 levels measured if thyroid-stimulating hormone (TSH) was below the reference range (RR; <0.27 miu/L) and free T4 was within or above the RR (12-22 pmol/L). Those with fully suppressed TSH (<0.02 mu/L) and high free T4 (>27 pmol/L) were defined as being over-replaced, while those with low, but measurable TSH and a normal free T4 were defined as unlikely to be over- replaced (control group). Receiver operating characteristic (ROC) curve analysis was used to assess the discriminant power of T3 to detect over-replacement. Of the 542 patients examined, 33 were included in the over-replaced group and 236 patients in the control group. A total of 273 patients were excluded for not fulfilling the criteria for either of these groups. In the over-replaced group, none had a raised T3. The most discriminant T3 level, using ROC curve analysis, was 1.6 nmol/L (RR=1.3-2.6 nmol/L), with a corresponding sensitivity and specificity of 58% and 71%, respectively (P=0.16). T3 levels bear little relation to thyroid status in patients on levothyroxine replacement, and normal levels can be seen in over-replaced patients. Measurement of T3 in this situation is of doubtful clinical value. WHAT'S ALREADY KNOWN ABOUT THIS TOPIC?: Thyroid function tests are the way that adequacy of levothyroxine replacement is determined. Where the test is available, T3 is often requested together with T4 and TSH by clinicians. The question is whether T3 measurement adds any further information. WHAT DOES THIS ARTICLE ADD?: The presented data supports the position that T3 measurement does not add anything to the interpretation of thyroid hormone levels in subjects with hypothyroidism on levothyroxine replacement therapy. Unnecessary testing could be avoided if this were more widely appreciated. In addition, over-replacement, with its attendant risks, would be more readily recognised and not wrongly excluded on the basis of a falsely reassuring normal T3 result.

People with Type Diabetes Mellitus (T1DM) self-reported views on their own condition management reveal links to potentially improved outcomes and potential areas for service improvement.

BACKGROUND: The self-management of type 1 diabetes (T1DM) has moved forward in many areas over the last 40 years. Our study asked people with T1DM what is their experience of blood glucose (BG) monitoring day to day and how this influences decisions about insulin dosing. METHODS: An on-line self-reported questionnaire containing 44 questions prepared after consultation with clinicians and patients was circulated to people with T1DM 116 responders provided completed responses. Fixed responses were allocated specific values (e.g. not confident = 0 fairly confident = 1). Multivariate regression analysis was carried out. Only those 5 factors with p-value <0.05 were retained. RESULTS: 59% of respondents were >50 years old and 66% had diabetes for >20 years, with 63% of patients reporting HbA1c results ≤8% or 64 mmol/mol. Findings included; 75% used only 1 m; 56% had used the same meter for ≥3 years; 10% had tried flash monitors; 47% were concerned about current BG level; 85% were concerned about long-term impact of higher BG. 72% of respondents keep BG level high to avoid hypoglycaemia; 25% used ≥7 mmol/L as pre-meal BG target to calculate dose; 65% were concerned they might be over/under-dosing; 83% did not discuss accuracy when choosing meter. However 85% were confident in their meter's performance. The factors that linked to LOWER HbA1c included LESS units of basal insulin (p < 0.001), HIGHER number of daily BG tests (p = 0.008), LOWER bedtime blood glucose (p = 0.009), HIGHER patient's concern over long-term impact of high BG (BG) (p < 0.009 but LOWER patient's concern over current BG values (p = 0.009). The final statistical model could explain 41% of the observed variation in HbA1c. CONCLUSION: Many people still run their BG high to avoid hypoglycaemia. Concern about the longer-term consequences of suboptimal glycaemic control was associated with a lower HbA1c and is an area to explore in the future when considering how to help people with T1DM.

Local delivery of a recombinant adenoassociated vector containing a tumour necrosis factor alpha antagonist gene in inflammatory arthritis: a phase 1 dose-escalation safety and tolerability study.

OBJECTIVE: To examine the safety and tolerability of a single intra-articular injection of rAAV2-TNFR:Fc, an adenoassociated virus serotype 2 vector containing the cDNA for the human tumour necrosis factor-immunoglobulin Fc fusion gene (tgAAC94), in subjects with inflammatory arthritis. METHODS: In a double-blind, placebo-controlled, phase 1, dose-escalation study, 15 subjects with inflammatory arthritis (14 with rheumatoid arthritis and 1 with ankylosing spondylitis) not receiving tumour necrosis factor alpha (TNFalpha) inhibitors with persistent moderate (grade 2) or severe (grade 3) swelling in a target joint due to inflammatory arthritis received a single intra-articular injection of rAAV2-TNFR:Fc at 1 x 10(10) (n = 5) or 1 x 10(11) (n = 6) DNase resistant particles per ml joint volume or placebo (n = 4) into a knee (n = 14) or ankle (n = 1). Safety was assessed through adverse event monitoring. As a secondary objective, changes in injected joint tenderness and swelling scores, each measured on a four-point scale, were evaluated. RESULTS: Intra-articular injections of rAAV2-TNFR:Fc were well tolerated with no major safety issues. One event, mild knee pruritus, was considered probably related. Synovial fluid TNFR:Fc protein was not detected (nor expected) at the doses used. At 12 weeks after injection, a two-point decrease in swelling was noted in 2/11 and 2/4 subjects injected with rAAV2-TNFR:Fc and placebo, respectively. CONCLUSION: A single dose of intra-articular rAAV2-TNFR:Fc appears to be safe and well tolerated in subjects without concurrent systemic TNFalpha antagonist use. It is thus feasible to proceed with larger trials to further test the safety and efficacy of local TNFR:Fc gene transfer as a therapeutic modality for patients with inflammatory arthritis.

On the use of low-cost computer peripherals for the assessment of motor dysfunction in Parkinson's disease--quantification of bradykinesia using target tracking tasks.

The potential of computer games peripherals to measure the motor dysfunction in Parkinson's diseases is assessed. Of particular interest is the quantification of bradykinesia. Previous studies used modified or custom haptic interfaces, here an unmodified force feedback joystick and steering wheel are used with a laptop. During testing an on screen cursor moves in response to movements of the peripheral, the user has to track a continuously moving target (pursuit tracking), or move to a predetermined target (step tracking). All tasks use movement in the horizontal axis, allowing use of joystick or steering wheel. Two pursuit tracking tasks are evaluated, pseudo random movement, and a swept frequency task. Two step tracking tasks are evaluated, movement between two or between two of five fixed targets. Thirteen patients and five controls took part on a weekly basis. Patients were assessed for bradykinesia at each session using standard clinical measures. A range of quantitative measures was developed to allow comparison between and within patients and controls using analysis of variance (ANOVA). Both peripherals are capable of discriminating between controls and patients, and between patients with different levels of bradykinesia. Recommendations for test procedures and peripherals are given.

Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia.

People with schizophrenia are at greater risk of obesity, Type 2 diabetes, dyslipidaemia and hypertension than the general population. This results in an increased incidence of cardiovascular disease (CVD) and reduced life expectancy, over and above that imposed by their mental illness through suicide. Several levels of evidence from data linkage analyses to clinical trials demonstrate that treatment-related metabolic disturbances are commonplace in this patient group, and that the use of certain second-generation antipsychotics may compound the risk of developing the metabolic syndrome and CVD. In addition, smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall CVD risk. Management and minimization of metabolic risk factors are pertinent when providing optimal care to patients with schizophrenia. This review recommends a framework for the assessment, monitoring and management of patients with schizophrenia in the UK clinical setting.

Liquorice and soy sauce, a life-saving concoction in a patient with Addison's disease.

Addison's disease is a relatively common disorder to endocrinologists, but is rare and potentially fatal when presenting acutely. Treatment now involves replacement of glucocorticoids and mineralocorticoids with synthetic compounds, although historically patients took common salt and plant-based preparations. We describe the case of a 42-year-old woman who self-treated undiagnosed Addison's disease for several years with soy sauce and liquorice sticks. She presented with a four-week history of decreased energy, malaise and postural dizziness. Our patient described an unusual diet of liquorice sticks and soy sauce, consuming around 46 g of salt per week. There was a family history of Type 1 diabetes mellitus. Physical examination was unremarkable, although subsequent investigation confirmed Addison's disease. Liquorice provided glycyrrhizic acid and glycyrrhetinic acid, which act on 11-beta hydroxysteroid dehydrogenase enzymes. In this case, the net effect was potentiation of glucocorticoid action on renal mineralocorticoid receptors in the context of failing adrenocortical steroid production. The case highlights the importance of taking a dietary history to aid diagnosis.

Silent growth hormone secreting pituitary adenomas: IGF-1 is not sufficient to exclude growth hormone excess.

Circulating insulin-like growth factor-1 (IGF-1) is increasingly being used as a screening test and in ongoing monitoring of treated acromegaly. We here present three cases of women (two of whom were on the oestrogen containing contraceptive pill at the time of presentation) who had normal circulating IGF-1 and no overt clinical features of acromegaly at the time of their pituitary surgery. Postoperatively, all were confirmed to have growth hormone excess in keeping with the presence of active somatotroph pituitary adenomas. We suggest that for optimal patient management, formal evaluation of growth hormone status with oral glucose tolerance testing should ideally be performed on all individuals for whom pituitary surgery is planned.

Success Rates in a Diabetes Specialist Nurse-Led Education Programme: Re-setting the Glucostat.

Analysis of National Diabetes Audit data from 2011-2012 of newly diagnosed people with type 1 diabetes mellitus (DM) found low initial success rates in much of the UK at 20% on initial training, while an unusually high success rate of 75% achieving target HbA1C<58 mmol/mol (< 7.5%) was found in Cheshire (England average=40.8%). We present a review of the approach taken by the Cheshire Diabetes team in the 12 months following diagnosis. Between 2012 and 2013, 15 consecutive newly diagnosed people with type 1 DM were followed up for 18 months. All received support and advice by community Diabetes Specialist Nurses (DSNs) and Dieticians covering Central and Eastern Cheshire, UK. Mean±SD age at diagnosis was 23±3 years. The period of contact with the DSN service varied from 7-12 weeks. Baseline HbA1C of 99 mmol/mol [11.2%] (95% CI: 86-111 mmol/mol [10.0-12.3%]) declined by ~50% to 49 mmol/mol [6.6%] (41-57 mmol/mol [5.9-7.4%]; F=16.9, p<0.001) at 6 months and did not change between 6-12 months. Of those newly diagnosed with type 1 DM, 84.6% achieved a target HbA1C<58 mmol/mol (<7.5%) and 61.5% met a target<48 mmol/mol (<6.5%). There was no significant weight change during the study. The key elements of this bio-psycho-social approach by the DSN team included providing psychological support, patient engagement, demonstrating positive regard, gaining trust, identifying health-seeking behaviour, providing key decision-making skills and developing a self-management plan. This resulted in improvements in overall glycaemic control well above the national average without untoward weight gain. The UK National Diabetes Audit (2011-2012) in newly diagnosed type 1 diabetics in Cheshire, UK, showed a success rate at 6 months post-diagnosis of 75% achieving a target HbA1C<58 mmol/mol (<7.5%) compared with the national average of 40.8%. Initially thought to be erroneous, these excellent results were confirmed. The approach taken to achieve them is herein described.

A cross-sectional study to investigate long-term cognitive function in people with treated pituitary Cushing's disease.

INTRODUCTION: It has been proposed that exposure to high levels of endogenous steroids in untreated pituitary Cushing's disease damages hippocampal structures leading to impairment in learning and memory processes. We hypothesised that patients with treated pituitary Cushing's disease would perform significantly worse on tests of cognitive ability than those with nonfunctioning pituitary adenomas. DESIGN: Sixteen adults with pituitary Cushing's disease (PCD) and 16 adults with non-functioning pituitary adenomas (NFA) undertook the following comprehensive neuropsychological assessments: National Adult Reading Test (NART: premorbid abilities), California Verbal Learning Test (CVLT 2 UK: learning and recall), Stroop (executive functioning), Trail-Making Test (TMT: executive functioning and attention), Adult Memory and Information Processing Battery (AMIPB: Information Processing Speed and Story Recall subtests). RESULTS: There was no significant difference in premorbid IQ scores (NFA mean=101 SD=13; PCD mean=102, SD=13), in verbal learning nor any significant difference in the percentage of verbal material retained in story recall (AMIPB). Performance on higher executive tasks Stroop and TMT and on measures of information processing was similar. However, there were significant decrements between some mean scores for both groups and published normative data with a clear association between higher HADS depression scores and impaired objective memory and attention which was not specific to PCD. CONCLUSIONS: We found no difference in cognitive function between patients with PCD and NFA. The results suggest a discrepancy between patients' subjective perception of functional cognitive impairments and objective findings on psychometric testing and point to the influence of affective symptoms on cognitive performance, particularly in Cushing's disease.

Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome.

AIMS/HYPOTHESIS: IGFs and their binding proteins are increasingly recognised as important in understanding the pathogenesis of cardiovascular disease. Low IGFBP-1, particularly coupled with low IGF-I, is associated with increased cardiovascular risk. In relation to structural and regulatory parallels between IGFBP-1 and - 2 we have now examined the hypothesis that IGFBP-2 may be a marker for cardiovascular risk. METHODS: Fasting IGFBP-2, IGFBP-1, IGFBP-3, IGF-I, IGF-II, insulin, C-peptide, glucose, lipids, NEFAs, and HbA1c were measured in a cohort of 163 patients with type 2 diabetes. Individuals were categorised according to the presence or absence of the metabolic syndrome. RESULTS: Patients with the metabolic syndrome had a lower IGFBP-2 concentration. Low circulating IGFBP-2 was associated with elevated fasting glucose (rho = - 0.23, p = 0.003). IGFBP-2 correlated negatively with triglycerides (rho = - 0.19, p = 0.01) and LDL-cholesterol (rho = - 0.20, p = 0.01), and positively with insulin sensitivity (HOMA-S) (rho = 0.26, p = 0.02). Multivariate logistic regression demonstrated that low IGFBP-2 was independently associated with an increased risk of the metabolic syndrome (OR 0.31 [95 % CI 0.11 - 0.90]; p = 0.03). IGFBP-3 did not differ according to the presence or absence of metabolic syndrome. CONCLUSION/INTERPRETATION: Low IGFBP-2 is associated with multiple cardiovascular risk factors similarly to IGFBP-1. Such associations were not apparent for IGFBP-3. Lack of marked prandial regulation of IGFBP-2, in contradistinction to IGFBP-1, may make IGFBP-2 a more robust biomarker for identification of insulin-resistant individuals at high cardiovascular risk in epidemiological studies.