Prevalence, glucose control and relative survival of people with Type 2 diabetes in the UK from 1991 to 2013.

AIMS: To characterize the prevalence of Type 2 diabetes between 1991 and 2013 in the UK and to determine whether corresponding glucose control and survival had changed in the diabetic population during this period. METHODS: For this retrospective cohort study, people diagnosed with Type 2 diabetes between 1991 and 2013 were identified from the Clinical Practice Research Datalink (CPRD) and the annual point prevalence calculated. Mean HbA1c by year was estimated. The Cox proportional hazards model was used to calculate the risk of all-cause mortality by year for incident cases of Type 2 diabetes treated with glucose-lowering therapy. RESULTS: Crude prevalence of diagnosed Type 2 diabetes increased from 1.32% [95% confidence interval (95% CI) 1.30% to 1.34%] in 1991 to 4.54% (4.52% to 4.56%) in 2013. Mean HbA1c for people with diagnosed Type 2 diabetes was 71 mmol/mol (8.6%) in 1991, 59 mmol/mol (7.5%) in 2003 and 58 mmol/mol (7.5%) in 2013. For diagnosed Type 2 diabetes treated with glucose-lowering therapy, when compared with 1991, the hazard ratio for all-cause mortality was 0.33 (0.27-0.41) in 2013. CONCLUSION: The prevalence of diagnosed Type 2 diabetes trebled in the UK between 1991 and 2013. Improved survival in people with diagnosed Type 2 diabetes is likely to account, at least in part, for the increase in prevalence observed.

Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer.

AIMS: To evaluate the association between insulin exposure and all-cause mortality, incident major adverse cardiovascular events (MACE) and incident cancer in people with type 2 diabetes treated with insulin monotherapy. METHODS: For this retrospective study, people with type 2 diabetes who progressed to insulin monotherapy from the year 2000 were identified from the UK Clinical Practice Research Datalink. The risks of progression to serious adverse outcomes were compared using Cox proportional hazards models. In the main analysis, insulin exposure was introduced into the model as prescribed international units per kilogram per day, as a cumulative, continuous, annually updated, time-dependent covariable. RESULTS: A total of 6484 subjects with type 2 diabetes who progressed to treatment with insulin monotherapy from the year 2000 onwards were followed for a mean of 3.3 years. The event numbers were as follows: deaths, n = 1110; incident MACE, n = 342; incident cancers, n = 382. Unadjusted event rates were 61.3 deaths per 1000 person-years, 26.4 incident MACE per 1000 person-years and 24.6 incident cancers per 1000 person-years. The adjusted hazard ratios in relation to 1-unit increases in insulin dose were 1.54 [95% confidence interval (CI) 1.32-1.78] for all-cause mortality, 1.37 (95% CI 1.05-1.81) for MACE and 1.35 (95% CI 1.04-1.75) for cancer. CONCLUSIONS: There was an association between increasing exogenous insulin dose and increased risk of all-cause mortality, MACE and cancer in people with type 2 diabetes. The limitations of observational studies mean that this should be further investigated using an interventional study design.

Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality.

AIMS: To compare the risk of major adverse cardiovascular events (MACE) and mortality for combination therapies with metformin and either sulphonylurea (SU) or dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: Data were from the UK Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with combination therapies comprising metformin plus SU or DPP-4i 2007-2012. The co-primary endpoints were all-cause mortality and MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score. RESULTS: A total of 33 983 patients were prescribed SU and 7864 DPP-4i, and 5447 patients in each cohort could be matched directly and 6901 by propensity score. In the main analysis, there were 716 MACE events and 1217 deaths. Crude event rates for MACE were 11.3 events per 1000 person-years (pkpy) for SU, versus 5.3 pkpy for DPP-4i. For all-cause mortality, rates were 16.9 versus 7.3 pkpy, respectively. Following adjustment, there was a significant increase in the adjusted hazard ratio (aHR) for all-cause mortality in those exposed to SU across all analytical models: aHR = 1.357 (95% CI 1.076-1.710) for all subjects, 1.850 (1.245-2.749) directly matched and 1.497 (1.092-2.052) propensity-matched. For MACE, aHR was 1.710 (1.280-2.285) for all subjects, 1.323 (0.832-2.105) directly matched and 1.547 (1.076-2.225) propensity-matched. CONCLUSIONS: There was a reduction in all-cause mortality for patients treated with metformin combined with DPP-4i versus metformin plus SU, and a similar trend for MACE.

Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study.

AIMS: To evaluate the risk of all-cause mortality and major adverse cardiovascular events (MACE) for patients exposed to first-line monotherapy with sulphonylurea or metformin. METHODS: Data were from the Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with metformin or sulphonylurea monotherapy as their first-line glucose-lowering regimen 2000-2012. The primary endpoint was all-cause mortality; the secondary endpoint was MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score. RESULTS: In the main analysis, 76 811 patients were prescribed metformin monotherapy (mean follow-up 2.9 years) and 15 687 sulphonylurea monotherapy (mean follow-up 3.1 years). A total of 2604 patients were included in each arm of the directly matched cohorts and 8836 in the propensity-matched. With respect to all-cause mortality, using all three analytical approaches the hazard ratio (HR) was significantly increased for sulphonylurea compared with metformin: adjusted HR = 1.580 (95% CI 1.483-1.684) for the main analysis, 1.902 (1.733-2.088) for those matched on propensity score, and 1.272 (1.021-1.584) for the directly matched cohort analysis. For MACE, the respective HRs were 1.196 (1.090-1.313), 1.202 (1.001-1.442) and 0.814 (0.578-1.148), respectively. CONCLUSIONS: All-cause mortality was significantly increased in patients prescribed sulphonylurea compared with metformin monotherapy. Whilst residual confounding and confounding by indication may remain, this study indicates that first-line treatment with sulphonylurea monotherapy should be reconsidered.

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls.

AIMS: Clinical and observational studies have shown an increased risk of cardiovascular events and death associated with sulphonylureas versus metformin. However, it has never been determined whether this was due to the beneficial effects of metformin or detrimental effects of sulphonylureas. The objective of this study was therefore to compare all-cause mortality in diabetic patients treated first-line with either sulphonylurea or metformin monotherapy with that in matched individuals without diabetes. METHODS: We used retrospective observational data from the UK Clinical Practice Research Datalink (CPRD) from 2000. Subjects with type 2 diabetes who progressed to first-line treatment with metformin or sulphonylurea monotherapy were selected and matched to people without diabetes. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables. RESULTS: We identified 78,241 subjects treated with metformin, 12,222 treated with sulphonylurea, and 90,463 matched subjects without diabetes. This resulted in a total, censored follow-up period of 503,384 years. There were 7498 deaths in total, representing unadjusted mortality rates of 14.4 and 15.2, and 50.9 and 28.7 deaths per 1000 person-years for metformin monotherapy and their matched controls, and sulphonylurea monotherapy and their matched controls, respectively. With reference to observed survival in diabetic patients initiated with metformin monotherapy [survival time ratio (STR) = 1.0], adjusted median survival time was 15% lower (STR = 0.85, 95% CI 0.81-0.90) in matched individuals without diabetes and 38% lower (0.62, 0.58-0.66) in diabetic patients treated with sulphonylurea monotherapy. CONCLUSIONS: Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first-line therapy and implies that metformin may confer benefit in non-diabetes. Sulphonylurea remains a concern.

Weight change in people with type 2 diabetes: secular trends and the impact of alternative antihyperglycaemic drugs.

AIM: This study aimed to describe the pattern of weight change in people with type 2 diabetes (T2DM) over time and when using alternative treatment regimens. METHODS: Data were from routine clinical practice in the UK. The weight trend was determined for each year from 1995 to 2010 for both prevalent and incident cases. Baseline weight was compared to absolute (mean Δ) and relative weights (% Δ) at 6, 12 and 24 months. RESULTS: Mean, standardized weight in prevalent cases increased from 83.4 to 92.1 kg for males and from 73.5 to 79.9 kg for females between 1995 and 2010 (p < 0.0001). For incident cases, the respective figures were 86.7 to 93.6 kg for males and 76.0 to 80.7 kg for females (p < 0.001). Between baseline and 6, 12 and 24 months, there were significant changes in weight for the majority of the treatment regimens selected for analysis. The largest weight increase at 12 months was for the patients who were prescribed a combination therapy with insulin and a thiazolidinedione, with a median increase of 4.1 kg (95% CI -0.60 to 8.0, p < 0.001). The largest weight decrease at 12 months was for the patients who were prescribed a combination therapy of metformin and exenatide, with a median decrease of -7.0 kg (95% CI -12.0 to -2.0, p < 0.001). CONCLUSIONS: There was a continual increase in body weight in people with T2DM over time, and considerable differences in the impact on weight using alternative treatment regimens. At the same time, glycaemic control remained relatively unchanged.

Estimated costs of acute hospital care for people with diabetes in the United Kingdom: a routine record linkage study in a large region.

AIMS: Diabetes represents a notable burden to health payers. The purpose of this study was to estimate acute hospital care costs of treating people with diabetes with reference to the costs of treating those without. METHODS: This was a retrospective study. Data from routine hospital practice were available from a large health region (439 000 people), with an estimated prevalence of diabetes of 3.4%. Common records were identified using probabilistic record linkage. Cost estimates were attributed to admissions using healthcare resource group software. Outpatient costs were attributed using published values. Data described are for 2004, and prices in pounds sterling for 2005. Standardised cost ratios were estimated to compare the costs observed in the diabetes population with those expected from the non-diabetic reference population. RESULTS: The total annual cost of admissions was pound28 944 811 per 100 000 people, of which pound3 650 869 per 100 000 (12.6%) was diabetes related. The standardised cost rate of inpatient treatment was 2.9. The total cost of outpatient attendances was pound6 589 971 per 100 000, of which pound711 431 per 100 000 (10.8%) was diabetes related. The standardised cost ratio for outpatient care was 4.1. The total cost of hospital care for patients with diabetes was pound11 206 986 per 100 000, or 12.3% of acute hospital expenditure. The combined standardised cost ratio was 3.1. Costs of care for inpatient treatment increased from 8.7% of revenue in 1994 to 12.3% in 2004. CONCLUSIONS: The costs of acute hospital care for treating people with diabetes increased markedly over a decade, and now exceed 12% of revenue.

The risk of cardiac failure following metal-on-metal hip arthroplasty.

AIMS: The aim of this study was to determine whether patients with metal-on-metal (MoM) arthroplasties of the hip have an increased risk of cardiac failure compared with those with alternative types of arthroplasties (non-MoM). PATIENTS AND METHODS: A linkage study between the National Joint Registry, Hospital Episodes Statistics and records of the Office for National Statistics on deaths was undertaken. Patients who underwent elective total hip arthroplasty between January 2003 and December 2014 with no past history of cardiac failure were included and stratified as having either a MoM (n = 53 529) or a non-MoM (n = 482 247) arthroplasty. The primary outcome measure was the time to an admission to hospital for cardiac failure or death. Analysis was carried out using data from all patients and from those matched by propensity score. RESULTS: The risk of cardiac failure was lower in the MoM cohort compared with the non-MoM cohort (adjusted hazard ratio (aHR) 0.901; 95% confidence interval (CI) 0.853 to 0.953). The risk of cardiac failure was similar following matching (aHR 0.909; 95% CI 0.838 to 0.987) and the findings were consistent in subgroup analysis. CONCLUSION: The risk of cardiac failure following total hip arthroplasty was not increased in those in whom MoM implants were used, compared with those in whom other types of prostheses were used, in the first seven years after surgery. Cite this article: Bone Joint J 2018;100-B:20-7.

Use of 5% lidocaine medicated plasters for the treatment of pain in routine hospital practice: patient reported pain, functioning and satisfaction.

OBJECTIVE: 5% lidocaine medicated plasters are a topical option in the treatment of peripheral neuropathic pain, as monotherapy or as an adjunct to systemic medication. This study sought to determine the impact of lidocaine plaster use on self-reported pain, functioning and patient satisfaction within a large teaching hospital. RESEARCH DESIGN AND METHODS: Patients were selected from the pain and rheumatology outpatient departments in Cardiff, Wales (2008-9). Postal surveys were sent to patients prescribed lidocaine plaster asking whether patients currently used the plaster and, if not, reason for discontinuation. Patients were asked to record pain score before and after therapy initiation, percentage pain relief, duration of effectiveness and impact on functioning. MAIN OUTCOME MEASURES: Pain scores, pain relief and levels of functioning before and after treatment. RESULTS: A total of 850 surveys were dispatched; 408 (48.0%) responses received; 197 (48.3%) patients were current users at survey completion. Median pain score prior to plaster use was 8 (IQR 7-9). One month after initiation, median pain score was 6 (4-8, p < 0.001) overall and 5 (4-7, p < 0.001) for current users. Median pain relief, after initial month of plaster use, was 30% (10-60%) for all patients and 50% (30-70%) for current users, whilst pain relief at time of survey was 30% (0-60%) and 50% (30-70%), respectively. A total of 181 (93.3%) current users claimed the plasters were effective. All three measures of functioning were significantly improved in current users: sleep (63.3% versus 20.1%, p < 0.001), mood (59.2% versus 18.6%, p < 0.001) and activity level (50.0% versus 19.5%, p < 0.001). Median satisfaction was 5 (IQR 1-8) for all patients and 7 (5-9) for current plaster users. CONCLUSIONS: The results of this study need to be considered within the context of a self-reported survey. However, pain, functioning and patient satisfaction were significantly improved in current users of 5% lidocaine medicated plasters.

The financial costs of healthcare treatment for people with Type 1 or Type 2 diabetes in the UK with particular reference to differing severity of peripheral neuropathy.

AIMS: To characterize symptom severity of diabetic peripheral neuropathy (DPN) in people with diabetes and to characterize its association with healthcare resource use. METHODS: The study was undertaken in Cardiff and the Vale of Glamorgan, UK. A postal survey was posted to subjects identified as having diabetes. Demography, quality of life (EQ-5D and SF-36) and symptoms of neuropathy (NTSS-6 and QOL-DN) data were collected. These data were linked to routine healthcare data coded into healthcare resource groups (HRGs) and subsequently costed according to UK National reference costs. RESULTS: Survey responses were received from 1298 patients, a 32% response rate. For patients with a clinically confirmed diagnosis of DPN, the mean NTSS-6-SA score was 6.16 vs. 3.19 (P < 0.001). Duration of diabetes did not change across groups defined by severity of neuropathy symptoms, but mean HbA(1c) and body mass index values did increase with symptom severity (range 7.6-8.1%, P = 0.023; and 28.0-30.9 kg/m(2), P < 0.001, respectively). General linear modelling showed that the NTSS-6-SA score was a significant predictor of both annual health resource costs and yearly prescribed drug costs. On average, each 1-point increase in NTSS-6-SA score predicted a 6% increase in primary and secondary care costs and a 3% increase in log transformed drug costs. CONCLUSION: This study demonstrated that severity of DPN symptoms was associated with increased healthcare resource use, thus costs.

Characterization and comparison of health-related utility in people with diabetes with various single and multiple vascular complications.

AIMS: To characterize and compare health-related utility in a large cohort of patients treated in hospital with diabetes and with single and multiple comorbidities. METHODS: The study was conducted in Cardiff and the Vale of Glamorgan, UK. Health-related utility was measured using the EQ5D(index), a standardized instrument for measuring health outcome. Patients from the Health Outcomes Data Repository (HODaR) were surveyed by postal questionnaire 6 weeks post discharge for in-patients and during clinics for patients attending as out-patients between January 2002 and July 2005. Patients with diabetes were identified by a previous history of in-patient admission with diabetes or as an out-patient with diabetes recorded as a coexisting diagnosis. RESULTS: We identified 4502 patients with diabetes. Mean ages were 65.4 and 64.2 years for males and females, respectively. Of these, 2003 (45%) had no recorded vascular complication. Overall, the EQ5D(index) was 0.584 (sd 0.325) for males and 0.533 (sd 0.351) for females. For those without any vascular complications the mean EQ5D(index) was 0.735 (sd 0.288). In a general linear model, the presence of single and multiple complications had a detrimental impact on the EQ5D(index). CONCLUSION: The results of this study provide an indication of the true impact of diabetes in terms of health-related utility. There was a decrease in the mean EQ5D(index) for those with vascular complications. Economic models of diabetes that have used additive or multiplicative methods to assess utility in individuals with several complications may be unreliable, and direct measurements, such as this, are recommended.

The health-related utility and health-related quality of life of hospital-treated subjects with type 1 or type 2 diabetes with particular reference to differing severity of peripheral neuropathy.

AIMS/HYPOTHESIS: We characterised symptom severity of diabetic peripheral neuropathy (DPN) in people with diabetes, and correlated this with health-related utility and health-related quality of life. MATERIALS AND METHODS: The study was undertaken in Cardiff and the Vale of Glamorgan, Wales. A postal survey was mailed to a random sample of subjects identified as having diabetes. Data were collected on the symptoms of neuropathy using the Neuropathic Total Symptom Score (self-administered) (NTSS-6-6A) and on quality of life using the Quality of Life in Diabetes Neuropathy Instrument (QoL-DN), EueroQoL five dimensions (EQ5D) and Short Form 36 (SF36). Other information, such as demographics and self-reported drug use, was also collected. The anonymised data were linked to routine inpatient and outpatient healthcare data. RESULTS: Responses were received from 1,298 patients. For patients with a clinically confirmed diagnosis of DPN, the mean NTSS-6-SA score was 6.16 vs 3.19 in patients without DPN (p<0.001). Four categories of severity were defined, ranging from none to severe. All quality of life measures showed a deterioration between these groups: the EQ5D(index) fell from an average of 0.81 in those without symptoms to 0.25 in those with severe symptoms, the SF36 general health profile fell from 59.9 to 25.5 (p<0.001) and the QoL-DN increased from 25.8 to 48.1 (p<0.001). Multivariate models also demonstrated that this relationship remained after controlling for other factors. CONCLUSIONS/INTERPRETATION: This study demonstrated that severity of DPN symptoms was predictive of poor health-related utility and decreased quality of life. Furthermore, it provides detailed utility data for economic evaluation of treatment of typical diabetes-related morbidity states. Reducing DPN morbidity should be a priority.

Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population.

OBJECTIVE: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0-3.0 and to explore the relation between achieved INR control and clinical outcomes. DESIGN: Record linkage study of routine activity records and INR measurements. SETTING: Cardiff and the Vale of Glamorgan, South Wales, UK. PARTICIPANTS: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INR measurements. MAIN OUTCOME MEASURES: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring. RESULTS: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range. CONCLUSIONS: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.

Evaluation of the association between the EQ-5D (health-related utility) and body mass index (obesity) in hospital-treated people with Type 1 diabetes, Type 2 diabetes and with no diagnosed diabetes.

AIMS: The purpose of this study was to characterize the impact of body mass index (BMI) on health-related utility for patients with Type 1 and Type 2 diabetes and those without diabetes. METHODS: The study was conducted in Cardiff and the Vale of Glamorgan, Wales, UK. Health-related utility was measured using the EQ-5D(index). Patients from the Health Outcomes Data Repository (HODaR) were surveyed by postal questionnaire either 6 weeks post discharge for in-patients or at out-patient clinics between January 2002 and July 2003. BMI was calculated from self-reported data within the survey. Patients with diabetes were identified by a previous history of an in-patient admission with diabetes or as an out-patient with diabetes recorded as a coexisting diagnosis. RESULTS: Questionnaires were returned from 27 924 patients of whom 2575 had diabetes. Increasing BMI was found to reduce utility in all three groups. BMI was significantly greater for those with Type 2 diabetes compared with those with Type 1, and those without diabetes (P < 0.001). Multiple regression analysis demonstrated that both BMI and diabetes status had a significant effect on utility. However, the rate of change of utility attributable to BMI was not found to be significantly different between the various groups. CONCLUSIONS: Obesity negatively impacts upon health-related utility and thus quality of life for all patient groups. There was no significant difference in the effect of obesity on utility between those with and without diabetes.