Academic Unit of Diabetes

Sheffield, United Kingdom

Academic Unit of Diabetes

Sheffield, United Kingdom
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van Dieren S.,University of Sydney | van Dieren S.,University Utrecht | Kengne A.P.,University of Sydney | Kengne A.P.,University Utrecht | And 18 more authors.
Diabetes, Obesity and Metabolism | Year: 2014

Aims: The aim of this study was to assess associations between patient characteristics, intensification of blood glucose-lowering treatment through oral glucose-lowering therapy and/or insulin and effective glycaemic control in type 2 diabetes. Methods: 11140 patients from the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial who were randomized to intensive glucose control or standard glucose control and followed up for a median of 5years were categorized into two groups: effective glycaemic control [haemoglobin A1c (HbA1c)≤7.0% or a proportionate reduction in HbA1c over 10%] or ineffective glycaemic control (HbA1c>7.0% and a proportionate reduction in HbA1c less than or equal to 10%). Therapeutic intensification was defined as addition of an oral glucose-lowering agent or commencement of insulin. Pooled logistic regression models examined the associations between patient factors, intensification and effective glycaemic control. Results: A total of 7768 patients (69.7%), including 3198 in the standard treatment group achieved effective glycaemic control. Compared to patients with ineffective control, patients with effective glycaemic control had shorter duration of diabetes and lower HbA1c at baseline and at the time of treatment intensification. Treatment intensification with addition of an oral agent or commencement of insulin was associated with a 107% [odds ratio, OR: 2.07 (95% confidence interval, CI: 1.95-2.20)] and 152% [OR: 2.52 (95% CI: 2.30-2.77)] greater chance of achieving effective glycaemic control, respectively. These associations were robust after adjustment for several baseline characteristics and not modified by the number of oral medications taken at the time of treatment intensification. Conclusions: Effective glycaemic control was associated with treatment intensification at lower HbA1c levels at all stages of the disease course and in both arms of the ADVANCE trial. © 2013 John Wiley & Sons Ltd.

Sheridan P.J.,Northern General Hospital | Marques J.L.B.,Federal University of Santa Catarina | Newman C.M.H.,Northern General Hospital | Heller S.R.,Academic Unit of Diabetes | Clayton R.H.,University of Sheffield
Europace | Year: 2010

Objective The aim of this study was to compare the rate-dependent measures of repolarization in patients with and without inducible ventricular arrhythmias, and so to assess the potential arrhythmogenic role of rate-dependent heterogeneities in cardiac repolarization.MethodsTwo groups of patients were studied during invasive electrophysiological procedures for standard clinical indications. A normal group (n = 17) with supraventricular tachycardia, structurally normal hearts and no inducible ventricular arrhythmias (PES-) and an inducible group (n = 13) with inducible ventricular arrhythmias (PES+). In each patient, we delivered a series of S1-S2 pacing sequences with a baseline S2 of 500 ms, which was progressively reduced. At the same time, a 12-lead electrocardiogram (ECG) was recorded. T-waves were extracted from each ECG recording, and 12 different T-wave measures were obtained from each patient across a range of coupling intervals. These included conventional measures, and those obtained from principal component analysis (PCA) of repolarization waveforms.ResultsAt baseline S2, there was no significant difference between the PES- and PES+ using conventional T-wave measures. There were significant differences at baseline S2 between groups using PCA-derived measures. These differences showed rate dependence and were larger at shorter coupling intervals. Two dynamic ECG measurements identified subjects who were inducible during PES; maximum relative T-wave residuum >0.10 (odds ratio: 38.5, 95 CI: 4.7-318.5; P < 0.001) and maximum T-wave shape index <0.007 (odds ratio: 180.0, 95 CI: 10.2-3167.0; P < 0.001).ConclusionT-wave shape index is rate dependent and discriminates between PES- and PES+ patients. We propose that patients with inducible arrhythmias have rate-dependent heterogeneity of repolarization which could be a useful tool for risk stratification. © 2009 The Author.

Choudhary P.,Academic Unit of Diabetes | Lonnen K.,Peninsula Medical School | Emery C.J.,Academic Unit of Diabetes | Freeman J.V.,University of Sheffield | And 2 more authors.
Diabetes Technology and Therapeutics | Year: 2011

Background: Continuous glucose monitoring devices measure interstitial glucose and are commonly used to investigate hypoglycemia. The relationship between interstitial glucose and blood glucose is not completely understood, particularly at low blood glucose concentrations. Interstitial glucose during hypoglycemia is generally lower than blood glucose in young subjects without diabetes and those with type 1 diabetes, but the effect of insulin resistance and obesity in type 2 diabetes on this relationship has not been examined previously. We studied the relationship between blood and interstitial glucose during experimental hypoglycemia in subjects with type 2 diabetes treated with insulin or sulfonylureas and matched controls without diabetes. Methods: Twenty subjects with type 2 diabetes (10 sulfonylurea-treated and 10 insulin-treated) and 10 controls without diabetes of similar age and weight underwent stepped hyperinsulinemic hypoglycemic clamps. We compared blood and interstitial glucose at different levels of hypoglycemia using random effects modeling. Results: Interstitial glucose was significantly higher than blood glucose at all levels of hypoglycemia (P<0.001), and this difference increased as glucose fell. For every 1 mmol/L drop in blood glucose, the difference increased by 0.32 mmol/L (P<0.001). This difference was not affected by presence of type 2 diabetes or by modality of treatment (P=0.10). Conclusions: In older subjects with or without type 2 diabetes, interstitial glucose is significantly higher than blood glucose, and this difference increases with increasing severity of hypoglycemia. Continuous glucose monitors may underestimate hypoglycemia in this group, and this should be taken into account when interpreting results obtained using this technology. © 2011 Mary Ann Liebert, Inc.

Peasgood T.,University of Sheffield | Brennan A.,University of Sheffield | Mansell P.,University of Nottingham | Elliott J.,Academic Unit of Diabetes | And 2 more authors.
Medical Decision Making | Year: 2016

Introduction. This study estimates health-related quality of life (HRQoL) or utility decrements associated with type 1 diabetes mellitus (T1DM) using data from a UK research program on the Dose Adjustment For Normal Eating (DAFNE) education program. Methods. A wide range of data was collected from 2341 individuals who undertook a DAFNE course in 2009-2012, at baseline and for 2 subsequent years. We use fixed- and random-effects linear models to generate utility estimates for T1DM using different instruments: EQ-5D, SF-6D, and EQ-VAS. We show models with and without controls for HbA1c and depression, which may be endogenous (if, for example, there is reverse causality in operation). Results. We find strong evidence of an unobserved individual effect, suggesting the superiority of the fixed-effects model. Depression shows the greatest decrement across all the models in the preferred fixed-effects model. The fixed-effects EQ-5D model also finds a significant decrement from retinopathy, body mass index, and HbA1c (%). Estimating a decrement using the fixed-effects model is not possible for some conditions where there are few new cases. In the random-effects model, diabetic foot disease shows substantial utility decrements, yet these are not significant in the fixed-effects models. Conclusion. Utility decrements have been calculated for a wide variety of health states in T1DM that can be used in economic analyses. However, despite the large data set, the low incidence of several complications leads to uncertainty in calculating the utility weights. Depression and diabetic foot disease result in a substantial loss in HRQoL for patients with T1DM. HbA1c (%) appears to have an independent negative impact on HRQoL, although concerns remain regarding the potential endogeneity of this variable. © The Author(s) 2016.

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