Are weight loss and metabolic outcomes of bariatric surgery influenced by candidate glucocorticoid receptor gene polymorphisms? A prospective study.

BACKGROUND: Bariatric surgery is the most effective treatment for severe obesity. There can be variation in the degree of weight reduction following bariatric surgery. It is unknown whether single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor locus (GRL) affect postoperative weight loss and metabolic outcomes. MATERIALS/METHODS: We studied the association between selected candidate SNPs and postoperative weight loss and metabolic outcomes in patients with severe obesity undergoing bariatric surgery. The polymorphisms rs41423247 (Bcl1), rs56149945 (N363S) and rs6189/rs6190 (ER22/23EK) were analysed. RESULTS: The 139 participants included 95 women (68.3%) and had a median (interquartile range) age of 53.0 (46.0-60.0) years and mean (SD) weight of 140.8 (28.8) kg and body mass index of 50.3 (8.6) kg/m2. At baseline, 59 patients had type 2 diabetes (T2D), 60 had hypertension and 35 had obstructive sleep apnoea syndrome treated with continuous positive airway pressure (CPAP). 84 patients (60.4%) underwent gastric bypass and 55 (39.6%) underwent sleeve gastrectomy. There were no significant differences in weight loss, glycated haemoglobin (HbA1c) or lipid profile categorized by genotype status, sex or median age. There was significant weight reduction after bariatric surgery with a postoperative BMI of 34.1 (6.8) kg/m2 at 24 months (p < 0.001). CONCLUSION: While GRL polymorphisms with a known deleterious effect on adipose tissue mass and function may have a small, additive effect on the prevalence of obesity and related metabolic disorders in the population, we suggest that the relatively weak biological influence of these SNPs is readily overcome by bariatric surgery.

Impact of Bariatric Surgery on Subtilisin/Kexin Type 9 (PCSK9) Gene Expression and Inflammation in the Adipose Tissue of Obese Diabetic Rats.

Bariatric surgery improves dyslipidaemia and reduces body weight, but it remains unclear how bariatric surgery modulates gene expression in fat cells to influence the proprotein convertase subtilisin/kexin type 9 (PCSK-9) and low-density lipoprotein receptor (LDLR) gene expression. The expression of the PCSK9/LDLR/tumor necrosis factor-alpha (TNFα) gene in adipose tissue was measured in two groups of Zucker Diabetic Sprague Dawley (ZDSD) rats after Roux-en-Y gastric bypass (RYGB) surgery or 'SHAM' operation. There was lower PCSK9 (p = 0.02) and higher LDLR gene expression (p = 0.02) in adipose tissue in rats after RYGB. Weight change did not correlate with PCSK9 gene expression (r = -0.5, p = 0.08) or TNFα gene expression (r = -0.4, p = 0.1). TNFα gene expression was positively correlated with PCSK9 gene expression (r = 0.7, p = 0.001) but not correlated with LDLR expression (r = -0.3, p = 0.3). Circulating triglyceride levels were lower in RYGB compared to the SHAM group (1.1 (0.8-1.4) vs. 1.5 (1.0-4.2), p = 0.038) mmol/L with no difference in cholesterol levels. LDLR gene expression was increased post-bariatric surgery with the potential to reduce the number of circulating LDL particles. PCSK9 gene expression and TNFα gene expression were positively correlated after RYGB in ZDSD rats, suggesting that the modulation of pro-inflammatory pathways in adipose tissue after RYGB may partly relate to PCSK9 and LDLR gene expression.

Saving the foot: Simple orthopaedic surgical intervention demonstrates improved outcomes and reduced costs.

BACKGROUND: Forefoot ulceration in diabetes requires significant resources, with high cost and low rates of success. The authors present the results of tendon procedures (percutaneous toe tenotomy and percutaneous tendo-achilles lengthening) under local anaesthetic to adjust mechanics in patients with diabetic neuropathic forefoot ulceration. METHODS: Retrospective review of electronic patient record of 19 patients (22 feet) undergoing local anaesthetic tendon procedures between April 2019 and April 2021 with a 12 month follow up period. Size of ulcer, rate of ulcer healing, complication rates and ulcer recurrence were recorded and compared to a population of conservatively-managed patients (14 patients, 15 feet) treated prior to the introduction of tendon procedures. All clinical information obtained from electronic patient records. RESULTS: All patients undergoing tendon procedures achieved complete ulcer healing at a mean time of 3.3 weeks for toe tip ulcers (after toe tenotomy) and 4.5 weeks for metatarsal head ulcers (after Achilles lengthening). There were no admissions for diabetic foot sepsis, reduced recurrence, reduced amputation rates and no mortality. Of the conservatively managed cohort, only 3 of the 15 achieved ulcer resolution without recurrence within the 12 month study period. The cohort managed conservatively had an average cost of £ 9902 per patient, per annum. The intervention cost was £ 1211 per patient, saving an average of £ 8691 per patient, per annum with ulcer resolution (88 % reduction in costs). CONCLUSION: Significant patient benefit, reduction in resource use and cost saving was seen with this simple intervention, which merits full evaluation in a clinical trial. LEVEL OF EVIDENCE: Level-IV.

Mortality in People with Type 2 Diabetes Following SARS-CoV-2 Infection: A Population Level Analysis of Potential Risk Factors.

INTRODUCTION: Research is ongoing to increase our understanding of how much a previous diagnosis of type 2 diabetes mellitus (T2DM) affects someone's risk of becoming seriously unwell following a COVID-19 infection. In this study we set out to determine the relative likelihood of death following COVID-19 infection in people with T2DM when compared to those without T2DM. This was conducted as an urban population study and based in the UK. METHODS: Analysis of electronic health record data was performed relating to people living in the Greater Manchester conurbation (population 2.82 million) who had a recorded diagnosis of T2DM and subsequent COVID-19 confirmed infection. Each individual with T2DM (n = 13,807) was matched with three COVID-19-infected non-diabetes controls (n = 39,583). Data were extracted from the Greater Manchester Care Record (GMCR) database for the period 1 January 2020 to 30 June 2021. Social disadvantage was assessed through Townsend scores. Death rates were compared in people with T2DM to their respective non-diabetes controls; potential predictive factors influencing the relative likelihood of admission were ascertained using univariable and multivariable logistic regression. RESULTS: For individuals with T2DM, their mortality rate after a COVID-19 positive test was 7.7% vs 6.0% in matched controls; the relative risk (RR) of death was 1.28. From univariate analysis performed within the group of individuals with T2DM, the likelihood of death following a COVID-19 recorded infection was lower in people taking metformin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 (GLP-1) agonist. Estimated glomerular filtration rate (eGFR) and hypertension were associated with increased mortality and had odds ratios of 0.96 (95% confidence interval 0.96-0.97) and 1.92 (95% confidence interval 1.68-2.20), respectively. Likelihood of death following a COVID-19 infection was also higher in those people with a diagnosis of chronic obstructive pulmonary disease (COPD) or severe enduring mental illness but not with asthma, and in people taking aspirin/clopidogrel/insulin. Smoking in people with T2DM significantly increased mortality rate (odds ratio of 1.46; 95% confidence interval 1.29-1.65). In a combined analysis of patients with T2DM and controls, multiple regression modelling indicated that the factors independently relating to a higher likelihood of death (accounting for 26% of variance) were T2DM, age, male gender and social deprivation (higher Townsend score). CONCLUSION: Following confirmed infection with COVID-19 a number of factors are associated with mortality in individuals with T2DM. Prescription of metformin, SGLT2is or GLP-1 agonists and non-smoking status appeared to be associated with a reduced the risk of death for people with T2DM. Age, male sex and social disadvantage are associated with an increased risk of death.

Methylation Status of Exon IV of the Brain-Derived Neurotrophic Factor (BDNF)-Encoding Gene in Patients with Non-Diabetic Hyperglycaemia (NDH) before and after a Lifestyle Intervention.

BDNF signalling in hypothalamic neuronal circuits is thought to regulate mammalian food intake. In light of this, we investigated how a lifestyle intervention influenced serum levels and DNA methylation of BDNF gene in fat tissue and buffy coat of NDH individuals. In total, 20 participants underwent anthropometric measurements/fasting blood tests and adipose tissue biopsy pre-/post-lifestyle (6 months) intervention. DNA was extracted from adipose tissue and buffy coat, bisulphite converted, and pyrosequencing was used to determine methylation levels in exon IV of the BDNF gene. RNA was extracted from buffy coat for gene expression analysis and serum BDNF levels were measured by ELISA. No differences were found in BDNF serum levels, but buffy coat mean BDNF gene methylation decreased post-intervention. There were correlations between BDNF serum levels and/or methylation and cardiometabolic markers. (i) Pre-intervention: for BDNF methylation, we found positive correlations between mean methylation in fat tissue and waist-hip ratio, and negative correlations between mean methylation in buffy coat and weight. (ii) Post-intervention: we found correlations between BDNF mean methylation in buffy coat and HbA1c, BDNF methylation in buffy coat and circulating IGFBP-2, and BDNF serum and insulin. Higher BDNF % methylation levels are known to reduce BNDF expression. The fall in buffy coat mean BDNF methylation plus the association between lower BDNF methylation (so potentially higher BDNF) and higher HbA1c and serum IGFBP-2 (as a marker of insulin sensitivity) and between lower serum BDNF and higher circulating insulin are evidence for the degree of BDNF gene methylation being implicated in insulinisation and glucose homeostasis, particularly after lifestyle change in NDH individuals.

Relationship between the Plasma Proteome and Changes in Inflammatory Markers after Bariatric Surgery.

Severe obesity is a disease associated with multiple adverse effects on health. Metabolic bariatric surgery (MBS) can have significant effects on multiple body systems and was shown to improve inflammatory markers in previous short-term follow-up studies. We evaluated associations between changes in inflammatory markers (CRP, IL6 and TNFα) and circulating proteins after MBS. METHODS: Sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics was performed on plasma samples taken at baseline (pre-surgery) and 6 and 12 months after MBS, and concurrent analyses of inflammatory/metabolic parameters were carried out. The change in absolute abundances of those proteins, showing significant change at both 6 and 12 months, was tested for correlation with the absolute and percentage (%) change in inflammatory markers. RESULTS: We found the following results: at 6 months, there was a correlation between %change in IL-6 and fold change in HSPA4 (rho = -0.659; p = 0.038) and in SERPINF1 (rho = 0.714, p = 0.020); at 12 months, there was a positive correlation between %change in IL-6 and fold change in the following proteins-LGALS3BP (rho = 0.700, p = 0.036), HSP90B1 (rho = 0.667; p = 0.05) and ACE (rho = 0.667, p = 0.05). We found significant inverse correlations at 12 months between %change in TNFα and the following proteins: EPHX2 and ACE (for both rho = -0.783, p = 0.013). We also found significant inverse correlations between %change in CRP at 12 months and SHBG (rho = -0.759, p = 0.029), L1CAM (rho = -0.904, p = 0.002) and AMBP (rho = -0.684, p = 0.042). CONCLUSION: Using SWATH-MS, we identified several proteins that are involved in the inflammatory response whose levels change in patients who achieve remission of T2DM after bariatric surgery in tandem with changes in IL6, TNFα and/or CRP. Future studies are needed to clarify the underlying mechanisms in how MBS decreases low-grade inflammation.

Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery.

Bariatric surgery (BS) results in metabolic pathway recalibration. We have identified potential biomarkers in plasma of people achieving type 2 diabetes mellitus (T2DM) remission after BS. Longitudinal analysis was performed on plasma from 10 individuals following Roux-en-Y gastric bypass (n = 7) or sleeve gastrectomy (n = 3). Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was done on samples taken at 4 months before (baseline) and 6 and 12 months after BS. Four hundred sixty-seven proteins were quantified by SWATH-MS. Principal component analysis resolved samples from distinct time points after selection of key discriminatory proteins: 25 proteins were differentially expressed between baseline and 6 months post-surgery; 39 proteins between baseline and 12 months. Eight proteins (SHBG, TF, PRG4, APOA4, LRG1, HSPA4, EPHX2 and PGLYRP) were significantly different to baseline at both 6 and 12 months post-surgery. The panel of proteins identified as consistently different included peptides related to insulin sensitivity (SHBG increase), systemic inflammation (TF and HSPA4-both decreased) and lipid metabolism (APOA4 decreased). We found significant changes in the proteome for eight proteins at 6- and 12-months post-BS, and several of these are key components in metabolic and inflammatory pathways. These may represent potential biomarkers of remission of T2DM.

Liothyronine and levothyroxine prescribing in England: A comprehensive survey and evaluation.

INTRODUCTION: The approach to thyroid hormone replacement varies across centres, but the extent and determinants of variation is unclear. We evaluated geographical variation in levothyroxine (LT4) and liothyronine (LT3) prescribing across General Practices in England and analysed the relationship of prescribing patterns to clinical and socioeconomic factors. METHODS: Data was downloaded from the NHS monthly General Practice Prescribing Data in England for the period 2011-2020. RESULTS: The study covered a population of 19.4 million women over 30 years of age, attending 6,660 GP practices and being provided with 33.7 million prescriptions of LT4 and LT3 at a total cost of £90million/year. Overall, 0.5% of levothyroxine treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019-2020. Factors strongly influencing more levothyroxine prescribing (model accounted for 62% of variance) were the CCG to which the practice belonged and the proportion of people with diabetes registered on the practice list plus antidepressant prescribing, with socioeconomic disadvantage associated with less levothyroxine prescribing. Whereas factors that were associated with increased levels of liothyronine prescribing (model accounted for 17% of variance), were antidepressant prescribing and % of type 2 diabetes mellitus individuals achieving HbA1c control of 58 mmol/mol or less. Factors that were associated with reduced levels of liothyronine prescribing included smoking and higher obesity rates. CONCLUSION: In spite of strenuous attempts to limit prescribing of liothyronine in general practice a significant number of patients continue to receive this therapy, although there is significant geographical variation in the prescribing of this as for levothyroxine, with specific general practice and CCG-related factors influencing prescribing of both levothyroxine and liothyronine across England.

Lifestyle intervention in individuals with impaired glucose regulation affects Caveolin-1 expression and DNA methylation.

AIMS: We investigated whether a lifestyle intervention could influence expression and DNA methylation of diabetes-related genes in patients with impaired glucose regulation (IGR), the results were compared to bariatric surgery, considering it an intensive change. METHODS: Twenty participants with IGR had adipose tissue biopsy and blood collected pre- and post-lifestyle (6 months) intervention; 12 obese patients had subcutaneous fat taken before and after bariatric surgery. RNA/DNA was extracted from all samples and underwent qPCR. DNA was bisulphite converted and 12 CpG sites of Caveolin-1 (CAV1) promoter were pyrosequenced. RESULTS: lifestyle intervention resulted in opposite direction changes in fat tissue and blood for CAV1 expression and DNA methylation and these changes were correlated between tissues, while no significative differences were found in CAV1 expression after bariatric surgery. CONCLUSIONS: Our findings suggest a role for CAV1 in modulating adipocyte function as a consequence of lifestyle changes, as exercises and diet. These results may provide insights into new therapeutic targets for diabetes prevention.

Screening for thyroid disease in patients with type 2 diabetes mellitus: An evaluation of current practice.

BACKGROUND: United Kingdom national guidelines do not recommend routine testing for thyroid disease in people with type 2 diabetes mellitus (T2DM). However, some studies suggest an increased risk of thyroid dysfunction in T2DM. The aim of this study was to evaluate the current practice of screening for thyroid disease in patients with T2DM. METHODS: Patients with pre-existing T2DM (n = 339) were selected from records for routine glycated haemoglobin testing performed in December 2008. Using routinely collected primary/secondary care data from 2009 to 2017, we examined longitudinal thyroid-stimulating hormone and free thyroxine requests to determine the overall proportion of patients screened for thyroid dysfunction and the time interval between thyroid tests requested. RESULTS: Thirty-three patients (9.7%) had pre-existing thyroid disease. Of the remaining 306 patients, 96.4% had at least one thyroid test during the follow-up period. When the time interval between tests was evaluated in these patients, there was a discrete peak in thyroid function test requests at 12 months, consistent with routine annual testing. Most requests (77%) originated from a general practice setting. CONCLUSIONS: Contrary to current guidelines, we have provided evidence suggestive of regular screening for thyroid dysfunction in patients with T2DM, particularly in general practice. The appropriateness of this practice remains unclear, but may warrant further examination to assess the clinical benefits of screening, balanced against cost.

Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan.

OBJECTIVES: We conducted a Pakistan-wide community-based survey on the prevalence of type 2 diabetes using glycated haemoglobin (HbA1c) as the screening test. The aim was to estimate diabetes prevalence across different demographic groups as well as all regions of Pakistan. DESIGN, SETTINGS AND PARTICIPANTS: Multistaged stratified cluster sampling was used for the representative selection of people aged ≥20 years, residing in 378 sampled clusters of 16 randomly selected districts, in this cross-sectional study. Eligible participants had blood drawn for HbA1c analyses at field clinics near to their homes. The oral glucose tolerance test (OGTT) was conducted on a subsample of the participants. Overall and stratified prevalence of type 2 diabetes and its association with risk factors were estimated using logistic regression models. MAIN OUTCOME MEASURES: Prevalence of prediabetes and type 2 diabetes. RESULTS: Of 18 856 eligible participants the prevalence of prediabetes was 10.91% (95% CI 10.46 to 11.36, n=2057) and type 2 diabetes was 16.98% (95% CI 16.44 to 17.51, n=3201). Overall, the mean HbA1c level was 5.62% (SD 1.96), and among newly diagnosed was 8.56% (SD 2.08). The prevalence was highest in age 51-60 years (26.03%, p<0.001), no formal education (17.66%, p<0.001), class III obese (35.09%, p<0.001), family history (31.29%, p<0.001) and female (17.80%, p=0.009). On multivariate analysis, there was a significant association between type 2 diabetes and older age, increase in body mass index and central obesity, positive family history, and having hypertension and an inverse relation with education as a categorical variable. On a subsample (n=1027), summary statistics for diagnosis of diabetes on HbA1c showed a sensitivity of 84.7%, specificity of 87.2% and area under the receiver operating characteristic curve 0.86, compared with OGTT. CONCLUSIONS: The prevalence of type 2 diabetes and prediabetes is much higher than previously thought in Pakistan. Comprehensive strategies need to be developed to incorporate screening, prevention and treatment of type 2 diabetes at a community level.

Assessment of global long interspersed nucleotide element-1 (LINE-1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2DM) individuals.

INTRODUCTION: Recent studies have indicated that methylation of the LINE-1 elements is associated with an increased risk of worsening carbohydrate metabolism. It has been shown that overall DNA methylation of LINE-1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors. METHODS: A total of 794 T2DM individuals from Salford, UK were included in this study (60% men n = 470). All patients had clinical and metabolic variables measured in 2002 (baseline outcomes) and annually through to 2016. Global LINE-1 DNA methylation was measured at four CpG sites. The QIAGEN PyroMark Q96 MD pyrosequencer was used to quantify methylation. RESULTS: The overall mean ± SD global LINE-1 methylation was 75.81 ± 3.25%. Cross-sectional linear regression analysis at baseline year 2002 showed that LINE-1 methylation was a significant predictor of diastolic BP (adjusted beta coefficient ß = -0.25), estimated glomerular filtration rate (eGFR) (ß = -0.48) and cholesterol HDL ratio (ß = -0.04). A 10% increase in LINE-1 methylation was associated with a lower diastolic BP by 2.5 mm Hg, a lower eGFR by 4.8 ml/min/1.73 m2 and decreased cholesterol/HDL ratio by 0.4 mmol/L. Longitudinal analysis over the 14-year-follow-up periods showed that global LINE-1 methylation at baseline was associated with lower BMI in women [ß = -0.25] and lower cholesterol: HDL ratio [ß = -0.07]. A 10% increase in LINE-1 methylation was associated with reduction in BMI by 2.5 kg/m2 in women and reduction in cholesterol:HDL ratio by 0.7 mmol/L. CONCLUSION: In a 14-year longitudinal cohort of T2DM individuals, relations between global LINE-1 DNA methylation status and specific metabolic markers were seen. Also, a higher degree of DNA methylation was predictive of less weight gain over time in women.

The pattern of prescribing of glucose modulating agents for type 2 diabetes in general practices in England 2016/17.

BACKGROUND: In the financial year 2016/17 there were 52.0 million items prescribed for diabetes at a total net ingredient cost of £983.7 million - up from 28.9 million prescription items and £572.4 million in 2006/07. Anti-diabetes drugs (British National Formulary section 6.1.2) make up 45.1 per cent of the total £983.7 million net ingredient cost of drugs used in diabetes and account for 72.0 per cent of prescription items for all diabetes prescribing. METHODS: We examined the way that agents licensed to treat type 2 diabetes were used across GP practices in England in the year 2016/2017. Analysis was at a GP practice level not at the level of patient data. RESULTS: Annual prescribing costs / patient / medication type for monotherapy varied considerable from £11/year for gliclazide and glimepiride to £885/year for Liraglutide. The use of SGLT-2i agents grew strongly at 70% per annum to around 100,000 DDD with prescriptions seen in 95% of GP practices. Liraglutide expenditure (11% of total) was high for a relatively small number of patients (1.3% of Defined Daily Doses), with still significant spend on exenatide. Liraglutide use significantly exceeded that of other glucagon-like peptide-1 (GLP-1) agonists. CONCLUSIONS: Our work demonstrates the significant cost of medication to modulate tissue glucose levels in type 2 diabetes and the dominance of some non-generic preparations in terms of number of prescriptions and overall spend. There are some older sulphonylureas in use, which should not generally be prescribed. Regular audit of patient treatment at a general practice level will ensure appropriate targeted use of licensed medications and of their cost effectiveness.

Social deprivation modifies the association between incident foot ulceration and mortality in type 1 and type 2 diabetes: a longitudinal study of a primary-care cohort.

AIMS/HYPOTHESIS: The aim of this study was to determine whether social deprivation in the presence of diabetes is an independent predictor of developing a foot ulcer and separately of mortality. METHODS: This was a primary-care-based retrospective analysis of 13,955 adults with type 1 (n = 1370) or type 2 (n = 12,585) diabetes after a median follow-up of 10.5 years. Demographic characteristics, indices of social deprivation and clinical variables were assessed at baseline. The primary outcomes were new foot ulceration (in those without a previous history of foot ulcers) and all-cause mortality. Cox proportional hazard models were used to describe the associations among foot ulceration, social deprivation and mortality. RESULTS: The mean age of the population was 69.4 (range: 16-89) years. The incidence of foot ulceration was greater in individuals with type 2 (8.6%) compared with type 1 diabetes (4.8%). Occurrence was similar by sex, but increased with age and deprivation index. Individuals in the highest quintile of deprivation were 77% more likely to develop a foot ulcer compared with those in the lowest quintile (OR 1.77 [95% CI 1.45, 2.14], p < 0.0001). Overall, 2946 (21.1%) deaths were recorded. Compared with individuals without a foot ulcer, the development of a foot ulcer was associated with a higher age- and sex-adjusted mortality rate (25.9% vs 14.0%), and a 72% (HR 1.72 [95% CI 1.56, 1.90], p < 0.001) increased risk of mortality in those with type 2 diabetes. Risk of death increased by 14% per quintile of deprivation in a univariable analysis (HR 1.14 [95% CI 1.10, 1.17]). In multivariable Cox regression analyses, there was a 48% increased risk of mortality in individuals with a foot ulcer (HR 1.48 [95% CI 1.33, 1.66]) independent of the Townsend index score (HR 1.13 [95% CI 1.10, 1.17], per quintile), baseline age, sex, diabetes type, smoking status, hypertension, statin use, ß-blocker use, metformin use, HbA1c levels and insulin use. CONCLUSIONS/INTERPRETATION: This study confirms the high mortality rate in individuals with diabetes-related foot ulcers. In addition, socioeconomic disadvantage was found to be an independent effect modifier, contributing to an increased burden of mortality in people with diabetes who develop foot ulceration. In light of this, and as diabetes service configurations are orientated for the next 5-10 years, modelling of foot ulceration risk needs to take socioeconomic disadvantage into account.

Polycystic ovarian syndrome: Assessment of approaches to diagnosis and cardiometabolic monitoring in UK primary care.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age. We examined the specific tests that are done in primary care to lead to the diagnosis of PCOS, and to support the diagnosis once made. METHODS: One thousand seven hundred and ninety-seven women were identified from a pooled GP practice database. The search included all patients defined with PCOS or related terms. Records included demographic information, medical history (diagnoses), blood test results and whether a pelvic ultrasound scan had been performed. RESULTS: The most common age of PCOS diagnosis was 20-29 years; 67.7% of the women had at least one concomitant Read-coded diagnosis. Most pelvic ultrasound scans were performed in the month immediately prior to diagnosis. In the 12 months prior to the diagnosis of PCOS being made, 30.5% of women underwent a measurement of their serum total testosterone level while 29.6% had their serum SHBG measured. For serum oestradiol, the corresponding statistics were 28.4%, LH 45.3% and for FSH 45.5% checked before diagnosis. Fasting blood glucose, random glucose and HbA1c were checked in 10.2%, 18.8% and 4.2%, of women before diagnosis, respectively, but in only 7.9%, 6.0% and 3.4% of women in the 24 months after diagnosis. There was a tendency for endocrine testing (oestradiol, LH, FSH, testosterone, SHBG) to peak in the weeks before diagnosis. For plasma glucose, testing was performed more evenly over time as for serum cholesterol. Of all women diagnosed with PCOS, 32.8% were prescribed metformin, 3.7% antihypertensives, 2.2% statins and 63.5% an oestrogen-containing contraceptive pill or HRT. CONCLUSION: The underlying pathophysiology of PCOS is still not fully understood. As a result, treatment is often focused on individual symptoms, not the syndrome itself. Robust laboratory led protocols would provide the necessary information to enable an appropriate diagnostic evaluation/cardometabolic monitoring.

BMI independently relates to glycaemia in patients with severe enduring mental illness (SMI).

BACKGROUND: People with severe mental illness (SMI) have higher rates of diabetes than the general population. AIMS: To assess the type-2 diabetes screening rates in primary care and the relation between body mass index (BMI) and dysglycaemia for patients on the SMI register in the Cheshire region of the United Kingdom. METHODS: The setting was 24 general practices in Central and Eastern Cheshire, United Kingdom. Subjects were identified through a semianonymized search of GP registers. RESULTS: About 451 of the 787 SMI patients were screened for dysglycaemia and dyslipidaemia. Fasting glucose was in the impaired fasting glycaemia range (6.1-6.9 mmol/l) in 6.5%, and indicative of type-2 diabetes (≥7.0 mmol/l) in 17.3%. There was a positive univariate relation between BMI and fasting glucose (normalized ß = 0.26, p < 0.001). In multivariate models, adjusting for age, gender, smoking and blood pressure, each unit increase in BMI [OR = 1.07 (1.01, 1.13); p = 0.031] and triglycerides [OR = 1.28 (1.06, 1.55); p = 0.009] were independently associated with an increased risk of having type-2 diabetes. CONCLUSION: Increasing BMI relates to dysglycaemia in patients with severe enduring mental illness (SMI). All patients with SMI whether or not receiving neuroleptic treatment should undergo routine monitoring of weight and metabolic parameters.