Nottinghamshire, United Kingdom
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Idris I.,University of Nottingham | Pillai A.,Sherwood Forest Hospitals Foundation Trust | Fernando D.J.,Sherwood Forest Hospitals Foundation Trust | Fernando D.J.,Sheffield Hallam University | And 2 more authors.
Diabetic Medicine | Year: 2013

Objectives: To describe baseline characteristics of responders to insulin therapy (HbA1c targets < 58 mmol/mol, 7.5%) at 18 months among adults with newly diagnosed diabetes. Methods: A retrospective UK study derived from 479 general practices electronic dataset. We included all adults (age > 18 years) with newly diagnosed diabetes who required insulin therapy within 6 months of diagnosis. The data comprised insulin regimen (long-acting only; premixed insulin only; basal bolus insulin regimen), gender, Townsend quintile, baseline and an 18-month measurement of clinical and biochemical variables. Multiple imputations were undertaken and logistic regression used to assess the effect of covariates. Results: A total of 1492 patients (aged 19-93 years) were analysed. Means (SD) baseline HbA1c and BMI were 10.3% (2.6%) and 29.6 (7.0%), respectively. Following multiple imputation for missing data, logistic regression analysis indicated important covariates to achieve HbA1c targets were baseline HbA1c, lipid lowering therapy, gender and age. Including all covariates, those treated with premixed insulin were 47% more likely to achieve target HbA1c at 18 months than those treated with a basal-bolus regimes (adjusted OR 1.47; 95% CI 1.12-1.92, P = 0.006)) and 32% more likely than those treated with long-acting insulin was (adjusted OR 1.32; 95% CI 1.01-1.74, P = 0.044). Those with a higher baseline HbA1c level, on lipid-lowering therapy, women and younger patients had a lower response rate. Mean weight gain (SD) was 2.4 kg (8.5 kg) and was not influenced by treatment regimen. Conclusion: The use of premixed insulin regimen among newly diagnosed patients with diabetes appears to be most effective in reaching HbA1c target values, independent of other confounders. The appropriate choice of insulin regimen at initiation should therefore take into account various metabolic and psychosocial factors. © 2012 Diabetes UK.

Idris I.,Sherwood Forest Hospitals Foundation Trust | Idris I.,University of Sheffield | Tate H.,Merck And Co. | Ahmad A.,Merck And Co. | McCormack T.,Whitby Group Practice
Journal of Clinical Lipidology | Year: 2011

Background: Apolipoprotein B (ApoB) is a superior predictor of low-density-lipoprotein (LDL) particle number and cardiovascular disease (CVD) risk compared with LDL-cholesterol (LDL-C) levels. Current evidence has shown a degree of discordance between LDL-C with ApoB levels among patients not receiving lipid-lowering therapy. The extent of this discordance among patients receiving LDL-lowering therapies however is less clear. Methods: We performed a post hoc analysis of the InPractice data looking at the concordance between LDL-C, non-high density lipoprotein-cholesterol (nonHDL-C) and total cholesterol with ApoB values. The study involved 786 high-risk CVD patients from 34 primary care centers initially treated with simvastatin (S) 40 mg at baseline subsequently randomized to adding ezetimibe 10 mg to S 40 mg (E/S40) or changed to atorvastatin (A) 40 mg or to rosuvastatin (R) 5-10 mg for 6 weeks. Results: At 6 weeks after treatment, the association between LDL-C and ApoB values for the different treatment regimes were similar; Pearson's correlation coefficients between LDL-C and ApoB were 0.84 (E/S40), 0.82 (A), and 0.83 (R). Overall, ApoB appeared to have a slightly greater correlation with nonHDL-C than with LDL-C across all treatment groups, for baseline and posttreatment values. The analysis of quintile frequencies showed a similar pattern; the proportion of patients who had values that fell in the same quintile post treatment for ApoB and LDL-C levels were 52.2% (E/S40), 44.5% (A), and 49.4% (R). Concordance between ApoB and nonHDL-C was 60.6% (E/S40), 62.4% (A), and 61.8% (R). Kappa analysis confirmed fair agreement between LDL-C and ApoB levels for all treatment groups; 0.59 (E/S40), 0.54 (A), and 0.56(R). Conclusion: We showed that the association between ApoB and LDL-C is similar across different lipid-lowering treatment regimes, which suggests that the use of different lipid-lowering agent confers similar ability to predict ApoB levels. When determining CVD risk at an individual patient level, limitation exists when using LDL-C or nonHDL-C per se as risk markers. In the absence of ApoB measurement, we believe that information from both LDL-C and nonHDL-C should be used together to improve the estimation of residual CVD risk among patients who are already receiving lipid lowering therapy. © 2011 National Lipid Association. All rights reserved.

Reeve D.,Nottinghamshire Healthcare NHS Trust | Gayson C.,Nottinghamshire Healthcare NHS Trust | Stephan T.,Sherwood Forest Hospitals Foundation Trust
Social Care and Neurodisability | Year: 2014

Purpose: The purpose of this paper is to increase awareness and compliance of The National Institute for Health and Care Excellence (NICE) Guidance regarding cognitive impairment in multiple sclerosis (MS). Design/methodology/approach: Assessments were offered routinely to consecutive inpatients with MS and to 20 per cent of outpatients. Once consent was gained, a cognitive assessment and subjective measure of cognition was completed with the patient, as well as a disability scale completed by the Medical Consultant. Individually targeted cognitive rehabilitation advice was provided using a bespoke advice leaflet. Afterwards, those who completed the assessment were asked to provide feedback on their experience. Findings: The percentage that were classed as below average cognitively and the pattern of impairment was comparable to previous findings. Memory was rated the most affected by the largest number of MS individuals and a strong relationship was found between objective and subjective measures of attention. The average functional disability level was rated at 6.99. Evaluations for the service provided were positive; over half of the sample was unaware of NICE Guidance on this issue but 100 per cent would recommend this service and provided optimistic quotes. Practical implications: This evaluation has enabled greater numbers to receive the recommended services and provided a useful baseline assessment of cognitive impairment and of patient attitudes towards this service. Resulting from this process, a new service framework has been proposed and presented at a local level. The advice leaflet developed for this process has been well received by patients and colleagues resulting in its submission to become an official NHS leaflet. Originality/value: Developed clinical governance of NHS services to patients with MS in offering improved assessment and management of cognitive problems. This is in contrast to the national trend showing little improvement of MS care and the lack of NICE implementation by the MS Trust and Royal College of Physicians audit. Furthermore, the bespoke advice leaflet developed for patients and carers of MS demonstrates originality of information provided. © Emerald Group Publishing Limited.

Owen V.,University of Nottingham | Seetho I.,Sherwood Forest Hospitals Foundation Trust | Idris I.,Sherwood Forest Hospitals Foundation Trust | Idris I.,University of Sheffield
Diabetes, Obesity and Metabolism | Year: 2010

Background: The effectiveness of insulin therapy to lower blood glucose levels in patients with type 2 diabetes (T2D) may depend on a variety of factors. This study aims to determine baseline parameters including body mass index (BMI) threshold that might predict responders to insulin therapy.Methods: This was a retrospective UK population-based study derived from 358 general practices electronic dataset. We included all patients with T2D, diagnosed at the age of >18 years old and who were initiated on insulin from January 2000 to December 2006. Insulin responders were defined as HbA1c <7.5% and/or HbA1c reduction by >1% at 12 months postinsulin initiation.Results: Results are expressed in mean (s.d.). A total of 6032 patients were identified. Baseline age was 63 years (11.7). In all, 61% of patients (3696) responded to insulin. At 1-year postinsulin initiation, HbA1c was significantly reduced (9.8 vs. 8.4%, p < 0.001) and weight increased (85.7 vs. 87.9 kg, p < 0.001). Using logistic regression model, older age (p < 0.001), lower BMI (p = 0.046), higher HbA1c (p < 0.001), basal-bolus insulin therapy and premixed insulin compared to basal insulin alone at baseline were independent predictors of responders to insulin. Gender and social class were not significant predictors of insulin responders. A BMI of <35.3 was derived as a cut-point for response to insulin (p = 0.038).Conclusion: Overall, insulin therapy confers significant HbA1c reduction and weight increase in patients with T2D. The responsiveness to insulin therapy however appears to depend on baseline age, BMI, HbA1c and insulin regime. Clinicians should take these factors into consideration when making a decision to initiate insulin therapy in patients with T2D. © 2010 Blackwell Publishing Ltd.

Objectives: Despite achieving desirable LDL cholesterol levels, the residual cardiovascular (CV) risk remains high among patients with diabetes. This is partly due to the increased number of atherogenic LDL particles and apoB levels, despite optimal LDL levels. As correlation studies have shown that non-HDL cholesterol is an acceptable surrogate marker for apoB, this study aimed to determine the concordance between non-HDL and LDL cholesterol in diabetic patients with different triglyceride and HbA 1c levels and metabolic syndrome (MS) status. Methods and results: Data from 11,005 diabetes patients from a large UK primary-care electronic database, with no previous CV events and not taking lipid-lowering therapy, were analyzed. Of the patients with LDL cholesterol <1.8mmol/L, only 58.6% had correspondingly low levels of non-HDL cholesterol (< 2.6mmol/L). Concordance between very low LDL and very low non-HDL values was significantly less among patients with high triglycerides (25.5%) compared with those with low triglycerides (76.2%) (Pearson's χ 2 test=177.6; P<0.001). However, greater concordance between very low LDL and very low non-HDL cholesterol levels was seen in patients without (77.9%), compared with those with (50.3%), the MS (Pearson's χ 2 test=59.7; P<0.001). This persisted even after adjusting for hypertriglyceridaemia. Concordance was similar at different levels of glycaemia. Conclusion: There was a significant discordance between LDL and non-HDL cholesterol levels in diabetes patients with high triglycerides or the MS. This might explain patients' high residual CV risk despite having achieved their desirable LDL cholesterol levels. Thus, treating both non-HDL and LDL cholesterol to achieve target values should be considered to reduce residual CV risk in patients with diabetes. © 2010 Elsevier Masson SAS.

Gunathilake W.,Sherwood Forest Hospitals Foundation Trust | Song S.,Northern General Hospital | Sridharan S.,Sherwood Forest Hospitals Foundation Trust | Fernando D.J.,Sherwood Forest Hospitals Foundation Trust | And 3 more authors.
QJM | Year: 2010

Background: Young patients (aged < 40 years) with type 2 diabetes (T2D) have a high lifetime risk of developing cardiovascular disease (CVD). However, little is known about the CVD risk profile of this cohort in the UK primary care setting.Aim: To determine CVD risk profile of young patients with T2D without CVD compared to older (aged >40 years) subjects. Design: A cross-sectional study using The Health Improvement Network (THIN) database, which contains anonymized patient information from more than 300 general practices throughout England and Wales. Methods: T2D subjects above the age of 18 years without previous CVD and not on lipid or blood pressure lowering therapy were randomly selected. Data on glycaemic control and CVD risk factors [weight, body mass index (BMI), lipid profile] were collected.Results: A total of 49 919 patients with T2D were identified, of whom 2756 (0.5%) and 47 163 (99.5%) were aged below and above 40 years, respectively. Despite being at least 30 years younger (mean age: early vs. later onset; 33.8 vs. 66.9 years, P < 0.001), the proportions of adverse CVD risk profiles for young patients were similar to the older cohort with T2D. For young vs. old patients: the prevalence of BMI >25: 84.4% vs. 85.3%, P = 0.77; total cholesterol >4 mmol/l: 53.4% vs. 53.8%, P = 0.76; systolic hypertension: 58.2 vs. 58.4%, P = 0.36 and diastolic hypertension: 28.1 vs. 28.5%, P = 0.73). Glycaemic controls were similarly suboptimal between the two groups (mean HbA1c: young vs. old; 7.6% vs. 7.5%, P = 0.49). The prevalence of risk factor clustering were also similar between young vs. old patients with T2D. Discussion: Young T2D subjects possess risk factors that confer high lifetime risk for macrovascular complications, and therefore merits aggressive cardioprotective treatment. © The Author 2010. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved.

Sellahewa L.,University of Nottingham | Sellahewa L.,Sherwood Forest Hospitals Foundation Trust | Simpson C.,Sherwood Forest Hospitals Foundation Trust | Maharajan P.,Sherwood Forest Hospitals Foundation Trust | And 2 more authors.
Clinical Ophthalmology | Year: 2014

Background: Digital retinal photography with mydriasis is the preferred modality for diabetes eye screening. The purpose of this study was to evaluate agreement in grading levels between primary and secondary graders and to calculate their sensitivity and specificity for identifying sight-threatening disease in an optometry-based retinopathy screening program. Methods: This was a retrospective study using data from 8,977 patients registered in the North Nottinghamshire retinal screening program. In all cases, the ophthalmology diagnosis was used as the arbitrator and considered to be the gold standard. Kappa statistics were used to evaluate the level of agreement between graders. Results: Agreement between primary and secondary graders was 51.4% and 79.7% for detecting no retinopathy (R0) and background retinopathy (R1), respectively. For preproliferative (R2) and proliferative retinopathy (R3) at primary grading, agreement between the primary and secondary grader was 100%. Where there was disagreement between the primary and secondary grader for R1, only 2.6% (n=41) were upgraded by an ophthalmologist. The sensitivity and specificity for detecting R3 was 78.2% and 98.1%, respectively. None of the patients upgraded from any level of retinopathy to R3 required photocoagulation therapy. The observed kappa between the primary and secondary grader was 0.3223 (95% confidence interval 0.2937-0.3509), ie, fair agreement, and between the primary grader and ophthalmology for R3 was 0.5667 (95% confidence interval 0.4557-0.6123), ie, moderate agreement. Conclusion: These data provide information on the safety of a community optometry-based retinal screening program for screening as a primary and as a secondary grader. The level of agreement between the primary and secondary grader at a higher level of retinopathy (R2 and R3) was 100%. Sensitivity and specificity for R3 were 78.2% and 98.1%, respectively. None of the false-negative results required photocoagulation therapy. © 2014 Sellahewa et al.

Pillai A.,Sherwood Forest Hospitals Foundation Trust | Warren G.,University of Nottingham | Gunathilake W.,Sherwood Forest Hospitals Foundation Trust | Idris I.,Sherwood Forest Hospitals Foundation Trust | Idris I.,University of Sheffield
Diabetes Technology and Therapeutics | Year: 2011

Background: Obstructive sleep apnea (OSA), a highly prevalent condition, is independently associated with increased risks of developing type 2 diabetes mellitus (T2D) and metabolic syndrome. It is unclear, however, if the severity of OSA has any impact on glycemic control among patients with T2D. We therefore aimed to determine the independent association between OSA severity and glycosylated hemoglobin (HbA1c) in patients with T2D. Methods: This was an observational cross-sectional study of 52 consecutive patients attending the diabetes obesity clinic between January 2008 to February 2010 with risk factors for sleep apnea and who underwent polysomnography study. Clinical, demographic, and lifestyle data were recorded using a questionnaire. Results: Prevalence of OSA in this clinical cohort was 58%. After adjusting for age, gender, body mass index, duration of diabetes, and insulin dose, increased severity of OSA was associated with increased HbA1c levels (P<0.014 for linear trend). A plateau effect between HbA1c and OSA severity was, however, noted from moderate to severe OSA levels. The adjusted mean values of HbA1c in each OSA category were 8.62% for none, 9.36% for mild, 10.61% for moderate, and 9.91% for severe. No significant associations were noted between liver transaminase level with OSA severity (P=0.324), between body mass index with OSA severity (P=0.278), or between HbA1c levels with the Epworth Score (a measure of daytime sleepiness) (P=0.46). Conclusions: Increased severity of OSA is independently associated with worsening glycemic control following adjustment of various confounders, including insulin dosage. We would hypothesize therefore that identification and treating OSA among patients with T2D may confer benefits in improving glycemic control. © Copyright 2011, Mary Ann Liebert, Inc.

Idris I.,Sherwood Forest Hospitals Foundation Trust | Idris I.,University of Nottingham | Abdulla H.,Sherwood Forest Hospitals Foundation Trust | Tilbrook S.,Sherwood Forest Hospitals Foundation Trust | And 2 more authors.
Journal of Sleep Research | Year: 2013

We investigate the effects of exenatide on excessive daytime sleepiness (EDS), driving performance and depression score in patients with type 2 diabetes with EDS. Eight obese patients with diabetes but without obstructive sleep apnoea (OSA) participated in a placebo-controlled single-blind study during which multiple wakefulness and sleep latency test, Epworth score, driving performance, depression score, fasting glucose and glycated haemoglobin (HbA1c) levels were assessed at baseline, end of placebo and treatment phase at baseline and after 22weeks of treatment. Mean (±standard error of the mean) age, body mass index (kgm2) and HbA1c [mmolmol-1 (%)] of patients at baseline were 50±4.9years, 37.6±1.1 and 65±19 (8.06±0.41), respectively. When compared to placebo, exenatide treatment was associated with a decrease in both subjective and objective sleepiness, based on the Epworth score reduction and the sleep latency increase assessed by multiple objective sleepiness and sustained attention (OSLER) tests, respectively. Mean sleep latency time (adjusted for change in HbA1c and weight) were 32.1±1.7, 29.1±1.7 and 37.7±1.7, respectively (P=0.002). Modelling for covariates suggested that improvement in mean sleep latency time is predicted by changes in weight (P=0.003), but not by changes in HbA1c (P=0.054). Epworth sleepiness score was reduced significantly (values for placebo versus exenatide: 11.3±1.2 versus 5.7±1.3; P=0.003). No significant change was noted in the depression score and driving performance. Exenatide is associated with a significant reduction in objective sleepiness in obese patients with type 2 diabetes without OSA, independent of HbA1c levels. These findings could form a basis for further studies to investigate the pathophysiological mechanisms of sleepiness in obese patients with type 2 diabetes. © 2012 European Sleep Research Society.

Idris I.,Sherwood Forest Hospitals Foundation Trust | Idris I.,University of Nottingham | Warren G.,Trent Research Design Service for the East Midlands | Donnelly R.,University of Nottingham
Archives of Internal Medicine | Year: 2012

Background: Findings of prior studies have been inconclusive about the ocular effects of thiazolidinediones on diabetic macular edema (DME). We evaluated, in patients with type 2 diabetes (T2D), the short-term and longterm risks of developing DME among users vs nonusers of thiazolidinediones. Methods: A retrospective cohort study of 103 368 patients with T2D and no DME at baseline using The Health Improvement Network (THIN) database. Clinical, biochemical, and demographic information was obtained for the period January 1, 2000, through November 30, 2009. Results: At 1 year, the incidence of DME was 1.3% (n=41) and 0.2% (n=227) among thiazolidinedione users (n=3227) and nonusers (n=100 141), respectively (odds ratio [OR], 5.7 [95% CI, 4.1-7.9]). After Cox multiple regression analysis (adjusted for age; systolic blood pressure; levels of lipids and hemoglobin A1c; and use of aspirin, fibrates, insulin, oral antidiabetic drugs, or reninangiotensin system blockers), multiple imputation analysis to adjust for missing values, and propensity score analysis to exclude for any selection bias, thiazolidinedione use was associated with an increased risk of DME at 1-year follow-up (OR, 2.3 [95% CI, 1.5-3.6]) and 10-year follow- up (hazard ratio [HR], 2.3; [95% CI, 1.7-3.0]). The effect was similar for pioglitazone and rosiglitazone. Combination therapy with insulin plus a thiazolidinedione was associated with a higher risk ofDMEafter propensity score adjustment (HR, 3.0 [95% CI, 1.5-5.9]), while aspirin use (HR, 0.6 [95% CI, 0.4-0.9]) and angiotensin-converting enzyme inhibitor use (HR, 0.4 [95% CI, 0.2-0.7]) were associated with a reduced risk of DME. Conclusion: Among patients with T2D, treatment with a thiazolidinedione was associated with an increased risk of DME at 1-year and 10-year follow-up evaluations.

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