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.

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.

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.

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.

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.

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.

BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment.

Excess deaths from cardiovascular disease are a major contributor to the significant reduction in life expectancy experienced by people with schizophrenia. Important risk factors in this are smoking, alcohol misuse, excessive weight gain and diabetes. Weight gain also reinforces service users' negative views of themselves and is a factor in poor adherence with treatment. Monitoring of relevant physical health risk factors is frequently inadequate, as is provision of interventions to modify these. These guidelines review issues surrounding monitoring of physical health risk factors and make recommendations about an appropriate approach. Overweight and obesity, partly driven by antipsychotic drug treatment, are important factors contributing to the development of diabetes and cardiovascular disease in people with schizophrenia. There have been clinical trials of many interventions for people experiencing weight gain when taking antipsychotic medications but there is a lack of clear consensus regarding which may be appropriate in usual clinical practice. These guidelines review these trials and make recommendations regarding appropriate interventions. Interventions for smoking and alcohol misuse are reviewed, but more briefly as these are similar to those recommended for the general population. The management of impaired fasting glycaemia and impaired glucose tolerance ('pre-diabetes'), diabetes and other cardiovascular risks, such as dyslipidaemia, are also reviewed with respect to other currently available guidelines.These guidelines were compiled following a consensus meeting of experts involved in various aspects of these problems. They reviewed key areas of evidence and their clinical implications. Wider issues relating to primary care/secondary care interfaces are discussed but cannot be resolved within guidelines such as these.

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.

Should Free Thyroxine Go Back into the Routine Thyroid Profile?

BACKGROUND: Many clinical chemistry laboratories offer thyroid-stimulating hormone (TSH) alone as a first-line test of thyroid function, and only reflex a free thyroxine (fT4) test if the TSH result is abnormal (i. e., outside of the laboratory reference range). In secondary hypothyroidism, a low fT4 may be accompanied by a low or a normal TSH level. A testing strategy that measures baseline TSH only risks missing cases of secondary hypothyroidism in which the TSH level is normal. METHODS: The current authors examined 26,106 consecutive thyroid function test (TFT) results in our initial analysis. If the TFT results were compatible with hypopituitarism, with fT4 below the reference range (9-20 pmol/L) and a TSH result ≤5 mU/L (reference range: 0.5-5 mU/L), the laboratory performed further tests of pituitary function. The cost of identifying pituitary insufficiency by measuring both fT4 and TSH was estimated for our population (in 2004 and 2013) and compared with 2 other relevant studies. RESULTS: A total of 121 patients had a normal TSH with a low fT4. 8 new cases of secondary hypopituitarism were identified when fT4 was combined with TSH as the front-line TFT profile. Of these, 5 were found to have pituitary adenomas, 2 of which were macroprolactinomas. The reagent cost of identifying each case by inclusion of fT4 in the TFT profile decreased from £11,568 (€16,089) in 1998 to £1451 (€2018) in 2013. CONCLUSIONS: 8 cases of pituitary insufficiency would not have been identified with a strategy of TSH testing alone, which calls for the addition of fT4 to the routine TFT profile. The cost per case of identifying those with pituitary insufficiency by additional measurement of fT4 has become cheaper with time.

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.

Socioeconomic deprivation independently predicts painful diabetic neuropathy in type 2 diabetes.

OBJECTIVE: Painful peripheral neuropathy in people with type 2 diabetes is a disabling complication. We explored associations of this condition with socioeconomic deprivation. RESEARCH DESIGN AND METHODS: The Townsend index of socioeconomic deprivation was examined in the pseudonymised GP records of 15388 (44.1% female) individuals with type 2 diabetes in the Cheshire county of England, and related to prevalence of drug treated painful diabetic neuropathy. We also analysed prescription trends with respect to pharmacotherapy for neuropathy pain relief. RESULTS: Treatment for neuropathic pain was initiated in 3 266 (21.2%) of patients. Those on treatment were older [68.2 (95% CI 67.8-68.7) vs. 66.6 (66.4-66.8) years] than those not on treatment. There was no difference in HbA1c (7%, 55 mmol/mol).There were significant differences between the groups for the Townsend deprivation index, with a greater proportion (30.6% vs. 22.8% of patients with treated neuropathic pain) having a score of ≥1 (Χ(2)=83.9, p<0.0001).Multivariate logistic regression analyses indicated that each unit increment in the Townsend index was associated with an 6% increased odds of requiring neuropathic pain treatment [odds ratio (95%CI) 1.06 (1.05-1.08), p<0.0001] independent of 5 year age band, BMI, gender, systolic BP, eGFR, HbA1C and total cholesterol. CONCLUSIONS: In this study using pseudonymised clinical records, a higher level of socioeconomic deprivation seemingly may predispose to severe neuropathic pain in diabetes requiring pharmacological intervention. Targeted allocation of healthcare resources to this group may offer clinical benefits.

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.

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.

Haemostatic factors, lipoproteins and long-term mortality in a multi-ethnic population of Gujarati, African-Caribbean and European origin.

OBJECTIVES: To examine the relations between haemostatic factors and lipoproteins with mortality in British Europeans, African-Caribbeans (AfC) and Gujarati Indians. METHODS: A prospective cohort study of 331 subjects (40-79 years), followed-up over 26 years for mortality. Apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), factor VII coagulant activity (FVIIc), fibrinogen and von Willebrand Factor (vWF) were measured at baseline in 118 Europeans, 100 AfC and 113 Gujaratis. Aortic pulse wave velocity (aPWV) was measured in 174 participants. RESULTS: 147 (44.4%) subjects died during a median of 24 years follow-up with 69 cardiovascular deaths. Women at baseline had higher, and AfC males the lowest FVIIc and Apo-A1 levels. Baseline age-sex and ethnicity adjusted FVIIc levels were higher in those who died (131.0 vs. 117.4%; P = 0.048). In similarly adjusted partial correlations, Apo-A1 was inversely related to arterial stiffness (ρ = -0.23, P = 0.04). Over the 26 years follow-up, participants below the median (i.e. with lower concentration) of FVIIc, Fibrinogen, Apo-B and vWF had better survival rates than those with higher concentrations; those with higher concentrations of Apo-A1 had better survival. In Cox multivariable regression analyses including sex, ethnicity and aPWV, independently increased risk of all-cause mortality came only from SBP (per 5 mmHg); P = 0.011), age (per year); P < 0.0001 and FVIIc at 7% (per 10-unit; HR 1.07 (1.02, 1.12); P = 0.008. Separately, Apo-A1 (HR 0.12 (0.02, 0.75; P = 0.029) was independently associated with a very significant 88% reduction in all-cause mortality. CONCLUSIONS: Despite a relatively small sample size, long-term follow-up suggests an independent effect of the prothrombotic state (via FVIIc) and apo-A1 (a constituent of HDL) on mortality.

IGF2 gene polymorphisms and IGF-II concentration are determinants of longitudinal weight trends in type 2 diabetes.

The hypothesis of the study was that IGF2 gene polymorphisms were associated with longitudinal trends in weight through modification of IGF-II concentration.Observational study that explored associations of the IGF2 gene and baseline circulating IGF-II concentration with 'real-world' longitudinal trends in body-mass index in a type 2 diabetes population.26 haplotype tagging single nucleotide polymorphisms (SNPs) from the IGF2 and H19 genes were studied in 485 Caucasian individuals in the Salford Longitudinal Diabetes Cohort. A generalised-estimating equation (GEE) model was used to separately study the association of SNPs and IGF-II concentration with 8-year longitudinal trends in body-mass index.High serum IGF-II concentration at baseline was associated with weight loss over the study period (ß=-0.006, 95% CI -0.009 to -0.002, p<0.001). 8 SNPs were associated with longitudinal body-mass index trends, of which 4 retained significance after multiple -testing correction. 2 SNPs rs10770063 and rs3842767 were associated with both IGF-II concentration as well as longitudinal weight changes.We report novel associations between polymorphisms in the IGF2 gene, with concentration of circulating IGF-II and also with longitudinal weight change in type 2 diabetes. Our data indicate that the IGF2 gene and its gene product may be important determinants of longitudinal weight trends in type 2 diabetes.