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Objective To assess the real-world cardiovascular (CV) safety for SU, in comparison with dipeptidylpeptidase-4 inhibitors (DPP4i) and thiazolidinediones (TZD) through development of robust methodology for causal inference in a whole nation study. Research Design and Methods A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was the composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction (MI), ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual endpoint and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial. Results Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91 to 1.09) from the multivariable Cox regression and 1.02 (0.91 - 1.13) and 1.03 (0.91- 1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94 - 1.13), 1.04 (0.93 - 1.17), and 1.03 (0.90 - 1.17). Conclusion Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.Article

OBJECTIVE To describe incidence of foot ulceration and amputation-free survival associated with foot ulceration status in a national population-based cohort study of people with diabetes. RESEARCH DESIGN AND METHODS The study population included 233,459 people with diabetes who were alive in Scotland on 1 January 2012 identified from the national population-based register (national prevalence 4.9%). Characteristics of patients identified from linked hospital and mortality records during follow-up to the end of November 2017 were compared by outcome. Cox regression was used to assess the association between history of foot ulcer and amputation-free survival. RESULTS The population included 23,395 people with type 1 diabetes and 210,064 people with type 2 diabetes. In total there were 13,093 (5.6%) people who had a previous foot ulceration, 9,023 people who developed a first ulcer, 48,995 who died, and 2,866 who underwent minor or major amputation during follow-up. Overall incidence of first-time foot ulcers was 7.8 per 1,000 person-years (95% CI7.6–7.9) and 11.2 (11.0–11.4) for any ulcer. Risk factors for reduced amputation-free survival included social deprivation, mental illness, and being underweight in addition to conventional cardiovascular risk factors. Adjusted hazard ratios (95% CI) were 2.09 (1.89–2.31) for type 1 diabetes and 1.65 (1.60–1.70) for type 2 diabetes. CONCLUSIONS The overall incidence of foot ulceration in a population-based study of people with diabetes was 11.2 per 1,000 person-years. Foot ulceration is associated with lower amputation-free survival rate, a potential measure of effectiveness of care among people with diabetes. Mental illness and social deprivation are also highlighted as risk factors.

Aims/hypothesis The aim of this work was to map the number of prescribed drugs over age, sex and area-based socioeconomic deprivation, and to examine the association between the number of drugs and particular high-risk drug classes with adverse health outcomes among a national cohort of individuals with type 1 diabetes. Methods Utilising linked healthcare records from the population-based diabetes register of Scotland, we identified 28,245 individuals with a diagnosis of type 1 diabetes on 1 January 2017. For this population, we obtained information on health status, predominantly reflecting diabetes-related complications, and information on the total number of drugs and particular high-risk drug classes prescribed. We then studied the association of these baseline-level features with hospital admissions for falls, diabetic ketoacidosis (DKA), and hypoglycaemia or death within the subsequent year using multivariate Cox proportional hazards models. Results Not considering insulin and treatment for hypoglycaemia, the mean number of prescribed drugs was 4.00 (SD 4.35). The proportion of individuals being prescribed five or more drugs at baseline consistently increased with age (proportion [95% CI]: 0–19 years 2.04% [1.60, 2.49]; 40–49 years 28.50% [27.08, 29.93]; 80+ years 76.04% [67.73, 84.84]). Controlling for age, sex, area-based socioeconomic deprivation and health status, each additional drug at baseline was associated with an increase in the hazard for hospitalisation for falls, hypoglycaemia and death but not for DKA admissions (HR [95% CI]: falls 1.03 [1.01, 1.06]; DKA 1.01 [1.00, 1.03]; hypoglycaemia 1.05 [1.02, 1.07]; death 1.04 [1.02, 1.06]). We found a number of drug classes to be associated with an increased hazard of one or more of these adverse health outcomes, including antithrombotic/anticoagulant agents, corticosteroids, opioids, antiepileptics, antipsychotics, hypnotics and sedatives, and antidepressants. Conclusions Polypharmacy is common among the Scottish population with type 1 diabetes and is strongly patterned by sociodemographic factors. The number of prescribed drugs and the prescription of particular high-risk drug classes are strong markers of an increased risk of adverse health outcomes, including acute complications of diabetes. Graphical abstract

Aims/hypothesis We aimed to examine whether crude mortality and mortality relative to the general population below 50 years of age have improved in recent years in those with type 1 diabetes. Methods Individuals with type 1 diabetes aged below 50 and at least 1 year old at any time between 2004 and 2017 in Scotland were identified using the national register. Death data were obtained by linkage to Scottish national death registrations. Indirect age standardisation was used to calculate sex-specific standardised mortality ratios (SMRs). Poisson regression was used to test for calendar-time effects as incidence rate ratios (IRRs). Results There were 1138 deaths in 251,143 person-years among 27,935 people with type 1 diabetes. There was a significant decline in mortality rate over time (IRR for calendar year 0.983 [95% CI 0.967, 0.998], p = 0.03), but the SMR remained approximately stable at 3.1 and 3.6 in men and 4.09 and 4.16 in women for 2004 and 2017, respectively. Diabetic ketoacidosis or coma (DKAoC) accounted for 22% of deaths and the rate did not decline significantly (IRR 0.975 [95% CI 0.94, 1.011], p = 0.168); 79.3% of DKAoC deaths occurred out of hospital. Circulatory diseases accounted for 27% of deaths and did decline significantly (IRR 0.946 [95% CI 0.914, 0.979], p = 0.002). Conclusions/interpretation Absolute mortality has fallen, but the relative impact of type 1 diabetes on mortality below 50 years has not improved. There is scope to improve prevention of premature circulatory diseases and DKAoC and to develop more effective strategies for enabling people with type 1 diabetes to avoid clinically significant hyper- or hypoglycaemia.

Aims/hypothesis We assessed the real-world effect of flash monitor (FM) usage on HbA1c levels and diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH) rates among people with type 1 diabetes in Scotland and across sociodemographic strata within this population. Methods This study was retrospective, observational and registry based. Using the national diabetes registry, 14,682 individuals using an FM at any point between 2014 and mid-2020 were identified. Within-person change from baseline in HbA1c following FM initiation was modelled using linear mixed models accounting for within-person pre-exposure trajectory. DKA and SHH events were captured through linkage to hospital admission and mortality data. The difference in DKA and SHH rates between FM-exposed and -unexposed person-time was assessed among users, using generalised linear mixed models with a Poisson likelihood. In a sensitivity analysis, we tested whether changes in these outcomes were seen in an age-, sex- and baseline HbA1c-matched sample of non-users over the same time period. Results Prevalence of ever-FM use was 45.9% by mid-2020, with large variations by age and socioeconomic status: 64.3% among children aged ≥65 years; and 54.4% vs 36.2% in the least-deprived vs most-deprived quintile. Overall, the median (IQR) within-person change in HbA1c in the year following FM initiation was −2.5 (−9.0, 2.5) mmol/mol (−0.2 [−0.8, 0.2]%). The change varied widely by pre-usage HbA1c: −15.5 (−31.0, −4.0) mmol/mol (−1.4 [−2.8, −0.4]%) in those with HbA1c > 84 mmol/mol [9.8%] and 1.0 (−2.0, 5.5) mmol/mol (0.1 [−0.2, 0.5]%) in those with HbA1c 1c were found in all age bands, sexes and socioeconomic strata, and regardless of prior/current pump use, completion of a diabetes education programme or early FM adoption. Variation between the strata of these factors beyond that driven by differing HbA1c at baseline was slight. No change in HbA1c in matched non-users was observed in the same time period (median [IQR] within-person change = 0.5 [−5.0, 5.5] mmol/mol [0.0 (−0.5, 0.5)%]). DKA rates decreased after FM initiation overall and in all strata apart from the adolescents. Estimated overall reduction in DKA event rates (rate ratio) was 0.59 [95% credible interval (CrI) 0.53, 0.64]) after FM vs before FM initiation, accounting for pre-exposure trend. Finally, among those at higher risk for SHH, estimated reduction in event rates was rate ratio 0.25 (95%CrI 0.20, 0.32) after FM vs before FM initiation. Conclusions/interpretation FM initiation is associated with clinically important reductions in HbA1c and striking reduction in DKA rate. Increasing uptake among the socioeconomically disadvantaged offers considerable potential for tightening the current socioeconomic disparities in glycaemia-related outcomes. Graphical abstract

Aims/hypothesis The aim of this work was to examine whether glycaemic control has improved in those with type 1 diabetes in Scotland between 2004 and 2016, and whether any trends differed by sociodemographic factors. Methods We analysed records from 30,717 people with type 1 diabetes, registered anytime between 2004 and 2016 in the national diabetes database, which contained repeated measures of HbA1c. An additive mixed regression model was used to estimate calendar time and other effects on HbA1c. Results Overall, median (IQR) HbA1c decreased from 72 (21) mmol/mol [8.7 (4.1)%] in 2004 to 68 (21) mmol/mol (8.4 [4.1]%) in 2016. However, all of the improvement across the period occurred in the latter 4 years: the regression model showed that the only period of significant change in HbA1c was 2012–2016 where there was a fall of 3 (95% CI 1.82, 3.43) mmol/mol. The largest reductions in HbA1c in this period were seen in children, from 69 (16) mmol/mol (8.5 [3.6]%) to 63 (14) mmol/mol (7.9 [3.4]%), and adolescents, from 75 (25) mmol/mol (9.0 [4.4]%) to 70 (23) mmol/mol (8.6 [4.3]%). Socioeconomic status (according to Scottish Index of Multiple Deprivation) affected the HbA1c values: from the regression model, the 20% of people living in the most-deprived areas had HbA1c levels on average 8.0 (95% CI 7.4, 8.9) mmol/mol higher than those of the 20% of people living in the least-deprived areas. However this difference did not change significantly over time. From the regression model HbA1c was on average 1.7 (95% CI 1.6, 1.8) mmol/mol higher in women than in men. This sex difference did not narrow over time. Conclusions/interpretation In this high-income country, we identified a modest but important improvement in HbA1c since 2012 that was most marked in children and adolescents. These changes coincided with national initiatives to reduce HbA1c including an expansion of pump therapy. However, in most people, overall glycaemic control remains far from target levels and further improvement is badly needed, particularly in those from more-deprived areas. Electronic supplementary material The online version of this article (10.1007/s00125-019-4900-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Background: Self-monitoring of blood glucose supported by the diabetes-app OneTouch Reveal® has demonstrated to improve HbA1c. We aimed at analyzing costs savings related the integration of telemedical features into diabetes management. Methods: Data from a randomized controlled trial were used to assess the 10-year risk of patients for fatal myocardial infarction (MI). On the basis of this risk assessments—also related to a 5% or 10% reduction of hypoglycemic episodes—cost savings for the health care systems of five European countries—France, Germany, Italy, Spain, and the United Kingdom—were modeled. Results: HbA1c reduction of 0.92% in insulin-treated type 2 diabetes patients (T2DM) was associated with a 2.3% decreased 10-year risk for fatal MI. In combination with a 10% reduction of hypoglycemic events this risk reduction led to cost savings of €16.1 million (France), €57.8 million (Germany), €30.9 million (Italy), €23.8 million (Spain), and €5.8 million (UK), considering all insulin-treated T2DM patients in the respective countries. Conclusion: Improving metabolic control and thus risk for comorbidities like MI by combining the glucose meter with CRI with telemedical features has the potential to reduce costs for European health care systems.

OBJECTIVE Whether advances in the management of type 1 diabetes are reducing rates of diabetic ketoacidosis (DKA) is unclear. We investigated time trends in DKA rates in a national cohort of individuals with type 1 diabetes monitored for 14 years, overall and by socioeconomic characteristics. RESEARCH DESIGN AND METHODS All individuals in Scotland with type 1 diabetes who were alive and at least 1 year old between 1 January 2004 and 31 December 2018 were identified using the national register (N = 37,939). DKA deaths and hospital admissions were obtained through linkage to Scottish national death and morbidity records. Bayesian regression was used to test for DKA time trends and association with risk markers, including socioeconomic deprivation. RESULTS There were 30,427 DKA admissions and 472 DKA deaths observed over 393,223 person-years at risk. DKA event rates increased over the study period (incidence rate ratio [IRR] per year 1.058 [95% credibility interval 1.054–1.061]). Males had lower rates than females (IRR male-to-female 0.814 [0.776–0.855]). DKA incidence rose in all age-groups other than 10- to 19-year-olds, in whom rates were the highest, but fell over the study. There was a large socioeconomic differential (IRR least-to-most deprived quintile 0.446 [0.406–0.490]), which increased during follow-up. Insulin pump use or completion of structured education were associated with lower DKA rates, and antidepressant and methadone prescription were associated with higher DKA rates. CONCLUSIONS DKA incidence has risen since 2004, except in 10- to 19-year-olds. Of particular concern are the strong and widening socioeconomic disparities in DKA outcomes. Efforts to prevent DKA, especially in vulnerable groups, require strengthening.

SHu reports grants from Health Protection Scotland during the conduct of the study. TMC reports grants from Diabetes UK (18/0005786). CR reports grants from Public Health Scotland and UK Research and Innovation. Background We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a cross-validated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. Methods In this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. Findings Of the total Scottish population on March 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5·8%), 1082 (0·3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89·8%) were aged 60 years or older. In the population without diabetes, 4081 (0·1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1·395 (95% CI 1·304–1·494; p

The RECOVERY (Randomised Evaluation of COVid‐19 thERapY) trial found that dexamethasone 6 mg once per day for 10 days reduced deaths by one‐third in ventilated patients and by one‐fifth in other patients, receiving oxygen therapy. This equates to the prevention of one death in around eight ventilated patients, or one in around 25 patients requiring oxygen.

The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient management need to be reorganised to maintain remote advice and support services, focusing on proactive care for the highest risk, and using telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision-making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.

Aims/hypothesis Our aim was to assess the use of continuous subcutaneous insulin infusion (CSII) in people with type 1 diabetes in Scotland and its association with glycaemic control, as measured by HbA1c levels, frequency of diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH), overall and stratified by baseline HbA1c. Methods We included 4684 individuals with type 1 diabetes from the national Scottish register, who commenced CSII between 2004 and 2019. We presented crude within-person differences from baseline HbA1c over time since initiation, crude DKA and SHH event-rates pre-/post-CSII exposure. We then used mixed models to assess the significance of CSII exposure, taking into account: (1) the diffuse nature of the intervention (i.e. structured education often precedes initiation); (2) repeated within-person measurements; and (3) background time-trends occurring pre-intervention. Results HbA1c decreased after CSII initiation, with a median within-person change of −5.5 mmol/mol (IQR −12.0, 0.0) (−0.5% [IQR −1.1, 0.0]). Within-person changes were most substantial in those with the highest baseline HbA1c, with median −21.0 mmol/mol (−30.0, −11.0) (−1.9% [−2.7, −1.0]) change in those with a baseline >84 mmol/mol (9.8%) within a year of exposure, that was sustained: −19.0 mmol/mol (−27.6, −6.5) (−1.7% [−2.5, −0.6]) at ≥5 years. Statistical significance and magnitude of change were supported by the mixed models results. The crude DKA event-rate was significantly lower in post-CSII person-time compared with pre-CSII person-time: 49.6 events (95% CI 46.3, 53.1) per 1000 person-years vs 67.9 (64.1, 71.9); rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.61 (95% credible interval [CrI] 0.47, 0.77; posterior probability of reduction pp = 1.00). The crude overall SHH event-rate in post-CSII vs pre-CSII person-time was also lower: 17.8 events (95% CI 15.8, 19.9) per 1000 person-years post-exposure vs 25.8 (23.5, 28.3) pre-exposure; rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.67 (95% CrI 0.45, 1.01; pp = 0.97). Conclusions/interpretation CSII therapy was associated with marked falls in HbA1c especially in those with high baseline HbA1c. CSII was independently associated with reduced DKA and SHH rates. CSII appears to be an effective option for intensive insulin therapy in people with diabetes for improving suboptimal glycaemic control. Graphical abstract

During the early stages of the COVID‐19 pandemic, hospitals in London, the UK epicentre, reported an unusually high number of people presenting with COVID‐19 disease developing diabetic ketoacidosis, hyperosmolar hyperglycaemic state, or a combination of both. Very high doses of insulin were often needed to manage the hyperglycaemia. It has been proposed that these metabolic disturbances may result from severe insulin resistance combined with decreased insulin secretion due to beta cell dysfunction.

The UK National Diabetes Inpatient COVID Response Group was formed at the end of March 2020 to support the provision of diabetes inpatient care during the COVID pandemic. It was formed in response to two emerging needs. First to ensure that basic diabetes services are secured and maintained at a time when there was a call for re-deployment to support the need for general medical expertise across secondary care services. The second was to provide simple safe diabetes guidelines for use by specialists and non-specialists treating inpatients with or suspected of COVID-19 infection. To date the group, comprising UK-based specialists in diabetes, pharmacy and psychology, have produced two sets of guidelines which will be continually revised as new evidence emerges. It is supported by Diabetes UK, the Association of British Clinical Diabetologists and NHS England.

The aim of this multi‐center, prospective, observer‐blinded, parallel group, randomized controlled trial was to assess the safety and efficacy of EDX110, a nitric oxide generating medical device, in the treatment of diabetic foot ulcers in a patient group reflecting “real world” clinical practice compared against optimal standard care. Participants were recruited from ten hospital sites in multidisciplinary foot ulcer clinics. The ulcers were full thickness, with an area of 25‐2500mm2 and either a palpable pedal pulse or ankle brachial pressure index >0.5. Infected ulcers were included. Treatment lasted 12 weeks, or until healed, with a 12‐week follow‐up period. Both arms were given optimal debridement, offloading and antimicrobial treatment, the only difference being the fixed used of EDX110 as the wound dressing in the EDX110 group. 135 participants were recruited with 148 ulcers (EDX110 ‐ 75; Control ‐ 73), 30% of which were clinically infected at baseline. EDX110 achieved its primary endpoint by attaining a median Percentage Area Reduction of 88.6% compared to 46.9% for the control group (p=0.016) at 12 weeks in the Intent to Treat population. There was no significant difference between wound size reduction achieved by EDX110 after 4 weeks and the wound size reduction achieved in the control group after 12 weeks. EDX110 was well tolerated. Thirty serious adverse events were reported (12 in the EDX110 group, of which 4 were related to the ulcer; 18 in the control group, of which 10 were related and 1 possibly related to the ulcer), with significant reduction in serious adverse events related to the ulcer in EDX group. There was no significant difference in adverse events. This study, in a real world clinical foot ulcer population, demonstrates the ability of EDX110 to improve healing, as measured by significantly reducing the ulcer area, compared to current best clinical practice. This article is protected by copyright. All rights reserved.

The majority of lower limb amputations are undertaken in people with peripheral arterial occlusive disease, and approximately 50% have diabetes. Quality of life is an important outcome in lower limb amputations; little is known about what influences it, and therefore how to improve it.The aim of this systematic review was to identify the factors that influence quality of life after lower limb amputation for peripheral arterial occlusive disease.MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science and Cochrane databases were searched to identify articles that quantitatively measured quality of life in those with a lower limb amputation for peripheral arterial occlusive disease. Articles were quality assessed by two assessors, evidence tables summarised each article and a narrative synthesis was performed.Systematic review.Twelve articles were included. Study designs and outcome measures used varied. Quality assessment scores ranged from 36% to 92%. The ability to walk successfully with a prosthesis had the greatest positive impact on quality of life. A trans-femoral amputation was negatively associated with quality of life due to increased difficulty in walking with a prosthesis. Other factors such as older age, being male, longer time since amputation, level of social support and presence of diabetes also negatively affected quality of life.Being able to walk with a prosthesis is of primary importance to improve quality of life for people with lower limb amputation due to peripheral arterial occlusive disease. To further understand and improve the quality of life of this population, there is a need for more prospective longitudinal studies, with a standardised outcome measure. Clinical relevance This is of clinical relevance to those who are involved in the rehabilitation of persons with lower limb amputations. Improved quality of life is associated with successful prosthetic use and focus should be directed toward achieving this.

Aims To describe the association between socio-economic status and mortality in a nation-wide cohort of people with type 1 diabetes in Scotland and to compare patterns over time and with the general population. Methods A retrospective cohort study was performed using data for people with type 1 diabetes from a population-based register linked to mortality records. Socio-economic status was derived from quintiles of an area-based measure: the Scottish Index of Multiple Deprivation. Sex-specific directly age-standardized mortality rates for each Scottish Index of Multiple Deprivation quintile and rate ratios comparing the most vs least deprived quintile were calculated for two time periods: 2006-2010 and 2011-2015. Data for the population without type 1 diabetes between 2011 and 2015 were available for comparison. Results Data for 3802 deaths among 33 547 people with type 1 diabetes were available. The age-standardized mortality rate per 1000 person-years decreased over time (from 2006-2010 to 2011-2015) for men and women with type 1 diabetes: 24.8 to 20.2 and 22.5 to 17.6, respectively. Mortality in populations with and without type 1 diabetes was generally higher for men than women and was inversely associated with socio-economic status. Rate ratios for the most vs least deprived groups increased over time among people with type 1 diabetes (men: 2.49 to 2.81; women: 1.92 to 2.86) and were higher than among populations without type 1 diabetes in 2011-2015 (men: 2.06; women: 1.66). Conclusions Socio-economic deprivation was associated with a steeper mortality gradient in people with type 1 diabetes than in the population without type 1 diabetes in Scotland. Age-standardized mortality has decreased over time but socio-economic inequalities may be increasing.

Background: The risks of, and risk factors for, COVID-19 disease associated with diabetes are poorly quantified brbrMethods: We identified as cases all th

Background and Aim: Costs for the treatment of diabetes and its comorbidities are a major international issue. A recent randomized clinical trial showed that the introduction of color range indicator (CRI)-based glucose meters (GMs) positively affects the HbA1c of patients with type 1 and type 2 diabetes, when compared to GMs without a CRI. This budget impact analysis aimed to translate this beneficial effect of CRI-based GMs, OneTouch Verio Flex and OneTouch Verio, into potential monetary impact for the healthcare systems of five European countries, Germany, Spain, Italy, France, and the United Kingdom. Material and Methods: Data from a randomized controlled trial, evaluating the effect of CRI-based GMs, were used to estimate the ten-year risk of patients for fatal myocardial infarction (MI) as calculated by the UK Prospective Diabetes Study (UKPDS) risk engine. On the basis of assessed risks for MI, the potential monetary impact for the healthcare systems in five European countries was modeled. Results: Based on a mean HbA1c reduction of 0.36%, as demonstrated in a randomized controlled trial, the UKPDS risk engine estimated a reduction of 2.4% of the ten-year risk of patients for fatal MI. When applied to our economic model, substantial potential cost savings for the healthcare systems of five European countries were calculated: €547 472 (France), €9.0 million (Germany), €6.0 million (Italy), €841 799 (Spain), and €421 069 (United Kingdom) per year. Conclusion: Improving metabolic control in patients with diabetes by the utilization of CRI-based GMs may have substantial positive effects on the expenditure of the healthcare systems of several European countries.

Aims/hypothesis Our aim was to investigate the geospatial distribution of diabetic foot ulceration (DFU), lower extremity amputation (LEA) and mortality rates in people with diabetes in small geographical areas with varying levels of multiple deprivation. Methods We undertook a population cohort study to extract the health records of 112,231 people with diabetes from the Scottish Care Information – Diabetes Collaboration (SCI-Diabetes) database. We linked this to health records to identify death, LEA and DFU events. These events were geospatially mapped using multiple deprivation maps for the geographical area of National Health Service (NHS) Greater Glasgow and Clyde. Tests of spatial autocorrelation and association were conducted to evaluate geographical variation and patterning, and the association between prevalence-adjusted outcome rates and multiple deprivation by quintile. Results Within our health board region, people with diabetes had crude prevalence-adjusted rates for DFU of 4.6% and for LEA of 1.3%, and an incidence rate of mortality preceded by either a DFU or LEA of 10.5 per 10,000 per year. Spatial autocorrelation identified statistically significant hot spot (high prevalence) and cold spot (low prevalence) clusters for all outcomes. Small-area maps effectively displayed near neighbour clustering across the health board geography. Disproportionately high numbers of hot spots within the most deprived quintile for DFU (p p p p Conclusions/interpretation In people with diabetes, DFU, LEA and mortality rates are associated with multiple deprivation and form geographical neighbourhood clusters.

Objective: \ud Lower extremity amputation (LEA) is more common in people from lower socio-economic groups. This study examined this further by investigating the influence of socio-economic status on mobility, participation, and quality of life (QoL) after LEA.\ud \ud Methods: \ud Prospective data were gathered for all LEAs performed in one year in one Scottish Health Board, commencing March 2014. A postcode derived Scottish Index of Multiple Deprivation (SIMD) was applied by quintile (SIMD 1 = most deprived). Routine data were collected on the cohort of 171 patients; 101 participants consented and received postal questionnaires on QoL (EQ-5D-5L), participation (Reintegration to Normal Living Index [RNLI]), and mobility (Prosthetic Limb User Survey of Mobility), six (n = 67) and 12 months (n = 50) after LEA.\ud \ud Results: \ud The mean ± SD age of the cohort was 66.2 ± 11.4 years; 75% were male and 53% had diabetes. In total, 67% lived in SIMD 1 and 2 and 11.1% in SIMD 5. Sixty per cent had a transtibial amputation. Mortality was 6% at 30 days 17% at six, and 29% at 12 months. Those in SIMD 1 were significantly younger (62.9 years) than those in SIMD 5 (76.3 years). Significantly more participants with a transfemoral amputation (TFA) lived in SIMD 1 (44%) compared with SIMD 5 (11%) (p = .004). Participation was low (RNLI scores: 6 months = 55.7; 12 months = 56.6) and PLUS M scores suggested mobility was poor overall at six (39.1) and 12 months (38.9). Mean QoL was 0.37 at 6 months and 0.33 at 12 months.\ud \ud Conclusion: \ud Although this study observed more LEAs in those from low socio-economic areas, it is impossible to conclude whether QoL after LEA is truly influenced by socio-economic status. There was an association between the disproportionately high rate of LEAs in SIMD groups 1 and 2 and the high prevalence of smoking, 61% vs. only 21% of those in the least deprived areas (SIMD 3, 4, and 5) being current smokers.

The aim of this multicenter, prospective, observer-blinded, parallel group, randomized controlled trial was to assess the safety and efficacy of EDX110, a nitric oxide generating medical device, in the treatment of diabetic foot ulcers in a patient group reflecting "real world" clinical practice compared against optimal standard care. Participants were recruited from ten hospital sites in multidisciplinary foot ulcer clinics. The ulcers were full thickness, with an area of 25-2,500 mm

BackgroundInsulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of pump therapy compared with MDI for adults with T1DM, with both groups receiving equivalent structured training in flexible insulin therapy.DesignPragmatic, multicentre, open-label, parallel-group cluster randomised controlled trial, including economic and psychosocial evaluations. After participants were assigned a group training course, courses were randomly allocated in pairs to either pump or MDI.SettingEight secondary care diabetes centres in the UK.ParticipantsAdults with T1DM for > 12 months, willing to undertake intensive insulin therapy, with no preference for pump or MDI, or a clinical indication for pumps.InterventionsPump or MDI structured training in flexible insulin therapy, followed up for 2 years. MDI participants used insulin analogues. Pump participants used a Medtronic Paradigm®VeoTM(Medtronic, Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK).Main outcome measuresPrimary outcome – change in glycated haemoglobin (HbA1c) at 2 years in participants whose baseline HbA1cwas ≥ 7.5% (58 mmol/mol). Key secondary outcome – proportion of participants with HbA1c≤ 7.5% at 2 years. Other outcomes at 6, 12 and 24 months – moderate and severe hypoglycaemia; insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being; qualitative interviews with participants and staff (2 weeks), and participants (6 months); and ICERs in trial and modelled estimates of cost-effectiveness.ResultsWe randomised 46 courses comprising 317 participants: 267 attended a Dose Adjustment For Normal Eating course (132 pump; 135 MDI); 260 were included in the intention-to-treat analysis, of which 235 (119 pump; 116 MDI) had baseline HbA1cof ≥ 7.5%. HbA1cand severe hypoglycaemia improved in both groups. The drop in HbA1c% at 2 years was 0.85 on pump and 0.42 on MDI. The mean difference (MD) in HbA1cchange at 2 years, at which the baseline HbA1cwas ≥ 7.5%, was –0.24% [95% confidence interval (CI) –0.53% to 0.05%] in favour of the pump (p = 0.098). The per-protocol analysis showed a MD in change of –0.36% (95% CI –0.64% to –0.07%) favouring pumps (p = 0.015). Pumps were not cost-effective in the base case and all of the sensitivity analyses. The pump group had greater improvement in diabetes-specific QoL diet restrictions, daily hassle plus treatment satisfaction, statistically significant at 12 and 24 months and supported by qualitative interviews.LimitationBlinding of pump therapy was not possible, although an objective primary outcome was used.ConclusionAdding pump therapy to structured training in flexible insulin therapy did not significantly enhance glycaemic control or psychosocial outcomes in adults with T1DM.Research priorityTo understand why few patients achieve a HbA1cof Trial registrationCurrent Controlled Trials ISRCTN61215213.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 20. See the NIHR Journals Library website for further project information.

To utilise whole-system analysis of capillary glucose measurement results to examine trends in timing of glucose monitoring, and to investigate whether these timings are appropriate based on observed patterns of hypoglycaemia.Near-patient capillary blood glucose results from eight acute hospitals collected over 57 months were analysed. Analysis of frequency of measurement, and measurements in the hypoglycaemic (4mmol/l) and severe hypoglycaemic (2.5mol/l) range per time of day was made.3345241 capillary glucose measurements were analysed. 1657594 capillary blood glucose values were associated with 106624 admissions in those categorised as having diabetes. Large peaks in frequency of glucose measurements occurred before meals, with the highest frequency of capillary glucose measurement activity being seen pre-breakfast. Overnight, an increase in measurement activity was seen each hour. This pattern was mirrored by frequency of measured hypoglycaemia. 27968 admissions (26.2%) were associated with at least one hypoglycaemic measurement. A greater proportion of measurements were within the hypoglycaemic range overnight with 61.7% of all hypoglycaemia between 2100 and 0900h, with peak risk of measured capillary glucose being hypoglycaemic between 0300 and 0400h.Hypoglycaemic is common with the greatest risk of hypoglycaemia overnight and a peak percentage of all readings taken being in the hypoglycaemic range between 0300 and 0400h. Measurement activity overnight was driven by routine, with patterns of proportion of measurements in the hypoglycaemic range indicating that there may be a significant burden of undiscovered hypoglycaemia in the patients not routinely checked overnight.

Background and Aims: Diabetes mellitus (DM), poor glycaemic control and raised body mass index (BMI) have been associated with postoperative complications in arthroplasty, although the relative importance of these factors is unclear. We describe the prevalence of DM in elective hip arthroplasty in a UK centre, and evaluate the impact of these factors. Methods: We analysed retrospective data for DM patients undergoing arthroplasty over a 6-year period and compared with non-diabetic matched controls (1 DM patient: 5 controls). DM was present in 5.7% of hip arthroplasty patients (82/1443). Results: Postoperative complications occurred in 12.2% of DM patients versus 12.9% of controls (p = 1.000); surgical complications were present in 6.1% of those with DM and 2.4% of controls (p = 0.087), while medical complications occurred in 8.5% of DM patients versus 10.7% of controls (p = 0.692). Complications developed in 23.1% of DM patients with poor glycaemic control (HbA1c > 53 mmol/mol) versus 9.8% with good control (p = 0.169). In DM patients and controls combined, complications occurred in 16.3% of obese patients versus 10.0% of non-obese patients (p = 0.043). In the DM cohort, 13.7% of overweight patients had complications versus 0% with a normal or low BMI (p = 0.587). Conclusions: DM rates were lower than expected, and glycaemic control was good. Overall complication rates were unrelated to the presence of DM or to glycaemic control, although surgical complications were observed more frequently in those with DM and poor glycaemic control was uncommon within our cohort. Complications were more frequent in those with a higher BMI. Whether some patients with DM but without an increased risk of complications are currently being excluded from surgery requires exploration.

Background: Diabetes mellitus is a leading cause of major lower extremity amputation. Objective: To examine the influence of gender, level of amputation and diabetes mellitus status on being fit with a prosthetic limb following lower extremity amputation for peripheral arterial disease. Study design: Retrospective analysis of the Scottish Physiotherapy Amputee Research Group dataset. Results: Within the cohort with peripheral arterial disease (n = 1735), 64% were men (n = 1112) and 48% (n = 834) had diabetes mellitus. Those with diabetes mellitus were younger than those without: mean 67.5 and 71.1 years, respectively (p

Summary objective Aldosterone synthase, a key enzyme in the terminal steps of aldosterone synthesis, is encoded by the CYP11B2 gene. A polymorphism in the 5′ coding region of this gene (−344 C/T) is associated with hypertension, particularly with elevation of the aldosterone to renin ratio. A second polymorphism (a conversion in intron 2 to resemble that of the neighbouring 11β-hydroxylase (CYP11B1) gene) is found in close linkage dysequilibrium with the variant at −344 C/T. The mechanism by which these variants predispose to cardiovascular disease and the precise intermediate phenotype associated with them remains speculative. design We performed a focused physiological study in normal volunteers stratified by CYP11B2 genotype. patients Twenty-three subjects homozygous for the T allele and 21 homozygous for the C allele of the −344 C/T polymorphism of CYP11B2 were studied. measurements Basal and angiotensin II stimulated plasma and 24-h urinary steroid excretion during low (60 mmol/day) and high (160 mmol/day) sodium intake and plasma steroids after ACTH stimulation were measured. results No influence of polymorphic variation on basal or stimulated plasma cortisol or aldosterone or other plasma steroid concentrations during either dietary phase was seen. However, excretion of tetrahydro-11-deoxycortisol (the urinary metabolite of 11-deoxycortisol), which is the precursor of cortisol) was increased in TT subjects during sodium restriction, consistent with impairment of zona fasciculata 11β-hydroxylation. conclusions We conclude that this polymorphism has no major influence on normal zona glomerulosa function but is associated with a change in 11β-hydroxylation in the zona fasciculata. The mechanism remains uncertain, but alteration of 11-deoxycortisol levels without change in cortisol suggests altered efficiency of 11β-hydroxylation. In the long term, this may lead to a minor but chronic increase in ACTH drive to the gland, which may have consequences for steroid synthesis and predispose to the risk of cardiovascular disease.

The HOPE study was a large, multi-centre study conducted in many countries, which recruited patients over the age of 55 who were at high cardiovascular risk, either because of the presence of existing vascular disease, or because of the presence of diabetes and at least one other cardiovascular risk factor. Ramipril reduced the end-point of cardiovascular death, myocardial infarction and stroke, and these effects were greater than could be explained by blood pressure lowering alone. Recent criticism has focused on slight differences in baseline risk factors between placebo and intervention groups, but these may have been incorrectly interpreted and the influence on the results exaggerated. It is now up to the reader, armed with differing interpretations of the same data, to return to the primary publications, read these and draw their own conclusions. The recently published PROGRESS study examined the use of perindopril plus or minus a diuretic in reducing the risk of recurrence of stroke in patients with a previous stroke. The results indicate benefit from blood pressure reduction in these patients, but no added benefit was seen with the use of an ACE inhibitor. Two other large studies on the use of ACE inhibitors in patients who are at high cardiovascular risk are currently under way. Copyright © 2002 John Wiley & Sons, Ltd. Practical Diabetes Int 2002; 19(6): 176–179

Recognising and accurately coding reversal of type 2 diabetes is key to improving outcomes and reducing healthcare costs, argue Louise McCombie and colleagues

Background Healthcare events related to diabetic foot disease carry a burden of morbidity, mortality and economic cost. Prompt identification of clinical infection with appropriate tissue sampling limits use of broad spectrum empirical antibiotics and improves antibiotic stewardship. Staphylococcus aureus remains the commonest infecting organism and high-dose flucloxacillin remains the empirical antibiotic of choice for antibiotic naive patients. Barriers to microbe-specific treatment include: adequate tissue sampling, delays in culture results, drug allergies and the emergence of multidrug-resistant organisms which can complicate the choice of targeted antibiotics. Even appropriate antibiotic treatment carries a risk of adverse events including the selection of resistant organisms. Aims Multidisciplinary clinical assessment of a diabetic foot infection is supported by the use of appropriate imaging modalities and deep tissue sampling, both of which are encouraged to enhance sampling accuracy. Narrow-spectrum, high dose, short duration antimicrobial therapy is ideal. Further clarity in these areas would be of benefit to clinicians involved in management of diabetic foot infections. Methods A combination of literature review with expert discussion was used to generate consensus on management of diabetic foot infection, with a specific focus on empirical antimicrobial therapy. Results Gram positive organisms represent the commonest pathogens in diabetic foot infection. However there are developing challenges in antimicrobial resistance and antibiotic availability. Discussion Recommendations for empirical therapy, including the choice of alternative oral agents and use of outpatient antibiotics would be of benefit to those involved in diabetic foot care. Conclusion This paper provides advice on empirical antibiotic therapy that may be used as a framework for local guideline development to support clinicians in the management of diabetic foot infection.

The insertion/deletion (I/D) polymorphism of the ACE gene accounts for 50% of the variation in serum ACE levels and activity. However, its functional significance with regard to diabetic complications and cardiovascular disease remains controversial. To review the literature assessing the significance of ACE gene polymorphism on the initiation and progression of diabetic complications and treatment implications, a systematic review of the Medline, Pubmed and EMBASE databases was performed. Keywords were 'diabetes mellitus', 'diabetic nephropathy', 'ACE gene polymorphism' and 'genotype', for the period 1966 to August 1999. Overall, ACE gene polymorphism appears to affect the progression of diabetic nephropathy, with individuals homozygous for the deletion allele (DD) having a shorter time period from the onset of microalbuminuria to renal replacement therapy and decreased survival thereafter. This may reflect relative resistance to ACE inhibitor therapy. There is no association between ACE gene polymorphism and retinopathy. Further large prospective studies are required to clarify the association of ACE gene polymorphism and diabetic complications. However, it appears that the deletion allele acts in a co-dominant manner as a susceptibility factor in the progression of diabetic nephropathy. ACE genotyping may therefore provide a simple method of identifying high risk individuals and allow the implementation of early and aggressive therapy.

Cardiovascular disease is a cause of premature morbidity and mortality in people with diabetes. Methods to reduce the burden of cardiovascular disease in diabetes have included control of glycaemia, reduction of conventional cardiovascular risk factors, and aggressive cardiological treatment for existing cardiovascular disease. ACE inhibitors have been used for control of hypertension, diabetic nephropathy, and for patients with a low ejection fraction. The Heart Outcomes Prevention Evaluation (HOPE) study examined the effects of 10 mg ramipril or placebo in 9297 high risk patients aged 55 or over. Diabetes was a pre-defined subgroup, and 3577 patient with diabetes were recruited who had evidence of vascular disease or had diabetes and one other cardiovascular risk factor (cholesterol>5.2, hypertension, microalbuminuria, smoking). The primary combined endpoint of myocardial infarction, stroke and cardiovascular death was significantly reduced by 25%, with a one third reduction in stroke. This reduction was seen both in patients with and without previous cardiovascular disease, and the benefit was greater than could be attributed to any decrease in blood pressure. The development of overt nephropathy was also reduced. This suggests that treatment with ramipril has vasculoprotective and renoprotective properties in people with diabetes, and should be prescribed or diabetic patients with existing cardiovascular disease or who have a high risk of disease because of the presence of cardiovascular risk factors. Copyright © 2000 John Wiley & Sons, Ltd.

OBJECTIVE To establish the incidence of nontraumatic lower-extremity amputation (LEA) in people with diabetes in Scotland. RESEARCH DESIGN AND METHODS This cohort study linked national morbidity records and diabetes datasets to establish the number of people with diabetes who underwent nontraumatic major and minor LEA in Scotland from 2004 to 2008. RESULTS Two thousand three hundred eighty-two individuals with diabetes underwent a nontraumatic LEA between 2004 and 2008; 57.1% (n = 1,359) underwent major LEAs. The incidence of any LEA among persons with diabetes fell over the 5-year study period by 29.8% (3.04 per 1,000 in 2004 to 2.13 per 1,000 in 2008, P < 0.001). Major LEA rates decreased by 40.7% from 1.87 per 1,000 in 2004 to 1.11 per 1,000 in 2008 (P < 0.001). CONCLUSIONS There has been a significant reduction in the incidence of LEA in persons with diabetes in Scotland between 2004 and 2008, principally explained by a reduction in major amputation.

Aims Current guidelines for lipid lowering as primary prevention advocate a treatment threshold 10-year coronary heart disease (CHD) risk of ≥ 30%. There is a variety of methods of calculating CHD risk, of varying complexity, which incorporate different factors. We aimed to determine if different methods of CHD risk calculation give different results and if a simpler method of CHD risk calculation could be developed for type 2 diabetes. Methods Using three recognised methods based on the Framingham equation, CHD risk was calculated for 200 consecutive patients with type 2 diabetes attending the clinic. A simple method of establishing those who should be treated with lipid-lowering agents was developed and sensitivity and specificity compared to the established method. Results Using method 1, only 58 (29%) of the patients would be above the treatment threshold; 108 (54%) with method 2; and 140 (70%) with method 3 ( 2=68.3, p < 0.001). Using the Glasgow Chart, sensitivity and specificity would be 100% and 85% respectively if patients are identified with total cholesterol ≥ 5.0 mmol/L plus two of: 1) age ≥ 50 years; 2) blood pressure ≥ 140/80 mmHg; 3) microalbuminuria. Conclusions It makes a significant difference which method is used to calculate CHD risk. Our simple method seems to be applicable to patients with type 2 diabetes, but requires confirmation in a larger population.

Older people with diabetes mellitus (DM) may be at high risk of falling because of general risk factors for falls as well as disease-specific factors.To determine the prevalence of falls and to investigate lower-limb factors for falls in older people with DM. Methods Sixty patients with DM over 55 years of age were recruited. 'Fallers' were those who self-reported at least one fall in the previous year. In addition to diabetes status and demographic information, the following were assessed: neuropathy symptom score (NSS), neuropathy disability score (NDS), foot deformity score (FDS), Tinetti performance-oriented assessment of mobility (POMA), ankle muscle strength and gait parameters. Data from 'fallers' and 'non-fallers' were compared and logistic regression analysis performed to identify variables predictive of falls.Thirty-five per cent (n = 21) of participants had fallen in the preceding year. Compared with 'non-fallers', there was a greater incidence of peripheral neuropathy among 'fallers' (86% of 'fallers' and 56% of 'non-fallers'), higher vibration perception threshold (P = 0.04), slower gait velocity (P0.001), lower muscle strength for dorsiflexion, plantarflexion, inversion and eversion (all P0.001) and higher incidence of bony prominences and prominent metatarsal heads (both P0.001). There was a strong and significant correlation between dorsiflexion muscle strength and gait velocity. Logistic regression analysis determined that walking velocity, strength of ankle dorsiflexors and NSS accurately predicted 75% of 'fallers'.Simple clinical measures of gait velocity and ankle muscle strength may be used to identify people with DM at risk of falling, allowing preventative strategies to be implemented.

Context Attempts to reduce doctors’ working hours and streamline postgraduate medical training may mean junior doctors’ out-of-hours experience is reduced. It is also proposed that, in the UK, compulsory clinical (Foundation Programme) competencies are to be accomplished in 1 year rather than 2 years as they are at present. This observational study was performed to examine the scope of opportunity available to junior doctors to achieve such competencies while working on a ‘Hospital at Night’ (H@N) team. Methods A database of electronic requests made to the H@N team was used to tabulate the number and type of tasks requested and to define differences between specialties, using local hospital admissions rates to contextualise the data. These requests were then compared with a list of compulsory clinical competencies to assess the scope of opportunity available to trainees to achieve these competencies when working on the H@N team. Results A total of 8268 referrals were made to our H@N team between 1 October 2007 and 31 January 2008 using the electronic Hospital Information System® (HIS®). The predefined, online HIS® request list included eight of the 20 tasks that represent compulsory competencies and showed that on average there were 247 opportunities per week of night shifts to perform them. Medical wards generated more requests than surgical wards (4767 versus 3170) and afforded greater opportunity to attain compulsory competencies (139 opportunities/week versus 96 opportunities/week; extra requests could not be attributed to either medical or surgical wards as original request did not include ward number). Conclusions The H@N initiative provides adequate opportunities for junior doctors to attain important clinical (Foundation) competencies. There appears to be sufficient opportunity to achieve these competencies within 1 year rather than the 2 years currently allowed in the UK Foundation Programme.

Aims: Hypoglycaemia confers excess morbidity and mortality. UK guidelines recommend capillary blood glucose (CBG) measurement is repeated 15 minutes following identification and treatment of CBG

Summary Aims The association of the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene with cardiovascular disease and diabetic nephropathy remains a controversial issue. This review aims to give an overview of the research to date assessing the impact of the ACE polymorphism in Type 1 and Type 2 diabetes mellitus (DM). Methods A systematic review of the literature was performed in the databases of MEDLINE, PubMed and EMBASE for the key words ‘diabetes mellitus’, ‘diabetic nephropathy’, ‘ACE polymorphism’ and ‘genotype’ and relevant articles were considered. Results A meta-analysis assessing the influence of the ACE polymorphism on disease susceptibility demonstrated significant odds ratios in individuals with the DD genotype for coronary heart disease, myocardial infarction and both diabetic and nondiabetic renal disease. No association was found for left ventricular hypertrophy or hypertension in nondiabetic subjects. Conclusions The ACE polymorphism appears to have a significant impact on the progression of diabetic nephropathy and may have therapeutic implications for identifying those individuals resistant to the effects of ACE inhibitors. It also appears to be indicative of an increased vascular risk in diabetic patients; however, larger prospective studies are required to clarify this situation.