Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021.

People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.

Management of adults with diabetes on the haemodialysis unit: summary of guidance from the Joint British Diabetes Societies and the Renal Association.

Diabetic nephropathy remains the principal cause of end-stage renal failure in the UK and its prevalence is set to increase. People with diabetes and end-stage renal failure on maintenance haemodialysis are highly vulnerable, with complex comorbidities, and are at high risk of adverse cardiovascular outcomes, the leading cause of mortality in this population. The management of people with diabetes receiving maintenance haemodialysis is shared between diabetes and renal specialist teams and the primary care team, with input from additional healthcare professionals providing foot care, dietary support and other aspects of multidisciplinary care. In this setting, one specialty may assume that key aspects of care are being provided elsewhere, which can lead to important components of care being overlooked. People with diabetes and end-stage renal failure require improved delivery of care to overcome organizational difficulties and barriers to communication between healthcare teams. No comprehensive guidance on the management of this population has previously been produced. These national guidelines, the first in this area, bring together in one document the disparate needs of people with diabetes on maintenance haemodialysis. The guidelines are based on the best available evidence, or on expert opinion where there is no clear evidence to inform practice. We aim to provide clear advice to clinicians caring for this vulnerable population and to encourage and improve education for clinicians and people with diabetes to promote empowerment and self-management.

Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care.

Diabetes is considered the commonest cause of end-stage renal disease. The increasing incidence of obesity and an ageing population, together, will lead to a greater number of people with diabetes associated with chronic kidney disease that could either be secondary to diabetic nephropathy or of different aetiology. Ageing and obesity influence approaches to the management of diabetes and accurate assessment of kidney disease. People with diabetes and chronic kidney disease consume a disproportionate component of expenditure on medical care. Guidelines on managing diabetes and kidney disease do not recognize the complex multi-morbid nature of the process. In addition to managing glycaemia and monitoring renal function, the assessment and management of cardiovascular disease risk factors and cardiovascular disease itself need to be factored into care. People with diabetes and diabetic nephropathy are more vulnerable to retinopathy and foot complications requiring coordinated care. People with diabetes and chronic kidney disease are more prone to anaemia and metabolic bone disease than those without diabetes at similar stages of chronic kidney disease, further increasing their vulnerability to acute complications from cardiovascular disease, foot emergencies and fractures. People with diabetes and chronic kidney disease are also more prone to hospitalization with infections and acute kidney injury. Given the 30-40% prevalence of kidney disease amongst people with diabetes, potentially >2% of the adult population would fit into this category, making it vital that new surveillance models of supported care are provided for those living with diabetes and kidney disease and for primary care teams who manage the vast majority of such people.

A national survey of the current state of screening services for diabetic retinopathy: ABCD-diabetes UK survey of specialist diabetes services 2006.

The main aims were to ascertain the progress made in the implementation of retinal screening services and to explore any barriers or difficulties faced by the programmes. The survey focused on all the essential elements for retinal screening, including assessment and treatment of screen-positive cases. Eighty-five per cent of screening programmes have a coordinated screening service and 73% of these felt that they have made significant progress. Eighty-five per cent of screening units use 'call and recall' for appointments and 73.5% of programmes follow the National Screening Committee (NSC) guidance. Although many units worked closely with ophthalmology, further assessment and management of screen-positive patients was a cause for concern. The fast-track referral system, to ensure timely and appropriate care, has been difficult to engineer by several programmes. This is demonstrated by 48% of programmes having waiting lists for patients identified as needing further assessment and treatment for retinopathy. Ophthalmology service for people with diabetic retinopathy was provided by a dedicated ophthalmologist in 89.4% of the programmes. Sixty-six per cent of the programmes reported inadequate resources to sustain a high-quality service, while 26% highlighted the lack of infrastructure and 49% lacked information technology (IT) support. In conclusion, progress has been made towards establishing a national screening programme for diabetic retinopathy by individual screening units, with a number of programmes providing a structured retinal screening service. However, programmes face difficulties with resource allocation and compliance with Quality Assurance (QA) standards, especially those which apply to ophthalmology and IT support. Screening programmes need to be resourced adequately to ensure comprehensive coverage and compliance with QA.

Diabetes specialist nurses and role evolvement: a survey by Diabetes UK and ABCD of specialist diabetes services 2007.

AIMS: To review the working practices of UK diabetes specialist nurses (DSNs), specific clinical roles, and to examine changes since 2000. METHODS: Postal questionnaires were sent to lead DSNs from all identifiable UK diabetes centres (n = 361). Quantitative and qualitative data were collected on the specific clinical roles, employment, and continual professional development of hospital and community DSNs, Nurse Consultants and Diabetes Healthcare Assistants. RESULTS: 159 centres (44%) returned questionnaires. 78% and 76% of DSNs plan and deliver education sessions compared with 13% in 2000 with a wider range of topics and with less input from medical staff. 22% of DSNs have a formal role in diabetes research compared with 48% in 2000. 49% of Hospital DSNs, 56% of Community DSNs and 66% of Nurse Consultants are involved in prescribing. 55% of DSNs carry out pump training, 72% participate in ante-natal and 27% renal clinics. 90% of services have independent diabetes nurse-led clinics. 93% of services have a dedicated Paediatric DSN. The mean number of children under the care of each PDSN is 109 (mode 120), which exceeds Royal College of Nursing recommendations. 48% of DSNs have protected time for continuing professional development of staff and 15% have a protected budget. One third of DSNs are on short-term contracts funded by external sources. CONCLUSIONS: The DSN role has evolved since 2000 to include complex service provision and responsibilities including specialist clinics, education of healthcare professionals and patients. The lack of substantive contracts and protected study leave may compromise these roles in the future.

Association of British Clinical Diabetologists (ABCD) and Diabetes-UK survey of specialist diabetes services in the UK, 2006. 1. The consultant physician perspective.

AIMS: To identify the views and working practices of consultant diabetologists in the UK in 2006-2007, the current provision of specialist services, and to examine changes since 2000. METHODS: All 592 UK consultant diabetologists were invited to participate in an on-line survey. Quantitative and qualitative analyses of responses were undertaken. A composite 'well-resourced service score' was calculated. In addition to an analysis of all respondents, a sub-analysis was undertaken, comparing localities represented both in 2006/2007 and in 2000. RESULTS: In 2006/2007, a 49% response rate was achieved, representing 50% of acute National Health Service Trusts. Staffing levels had improved, but remained below recommendations made in 2000. Ten percent of specialist services were still provided by single-handed consultants, especially in Northern Ireland (in 50% of responses, P = 0.001 vs. other nations). Antenatal, joint adult-paediatric and ophthalmology sub-specialist diabetes services and availability of biochemical tests had improved since 2000, but access to psychology services had declined. Almost 90% of consultants had no clinical engagement in providing community diabetes services. The 'well-resourced service score' had not improved since 2000. There was continued evidence of disparity in resources between the nations (lowest in Wales and Northern Ireland, P = 0.007), between regions in England (lowest in the East Midlands and the Eastern regions, P = 0.028), and in centres with a single-handed consultant service (P = 0.001). Job satisfaction correlated with well-resourced service score (P = 0.001). The main concerns and threats to specialist services were deficiencies in psychology access, inadequate staffing, lack of progress in commissioning, and the detrimental impact of central policy on specialist services. CONCLUSIONS: There are continued disparities in specialist service provision. Without effective commissioning and adequate specialist team staffing, integrated diabetes care will remain unattainable in many regions, regardless of reconfigurations and alternative service models.

Prediction of cardiovascular risk in people with diabetes.

People with diabetes are at high risk of cardiovascular morbidity and mortality, especially if they have already developed vascular problems. For patients who are apparently free of vascular complications, risk tables are often used to assess the risk of cardiovascular events in the following years, and to decide on treatment with statins or anti-platelet therapy. These risk prediction tables include estimates of traditional cardiovascular risk factors and are based on populations, some of which only contained a very small number of people with diabetes. Multiple problems can be identified with these tables, and many seriously underestimate cardiovascular risk in people with diabetes. Possible ways of addressing this include using risk estimation tools based solely on diabetic populations, adding in additional traditional variables such as triglycerides or left ventricular hypertrophy, including novel cardiovascular risk factors, or intervening at a lower level of estimated risk in people with diabetes compared with non-diabetic subjects. Alternatively, estimates of individual risk could be abandoned and all people with diabetes could be treated with statins and other effective agents.

Association of British Clinical Diabetologists (ABCD): survey of specialist diabetes care services in the UK, 2000. 2. Workforce issues, roles and responsibilities of diabetes specialist nurses.

AIM: To examine the provision and role of diabetes specialist nurses (DSNs), and the content of patient education programmes in the UK. METHOD: A postal survey of secondary care providers of diabetes services in the UK in 2000. RESULTS: Following two reminders, a 77% response rate demonstrated 2.5 (median) whole time equivalent DSNs per 250 000 population, with only 13% of centres meeting the recommended staffing level of four per 250 000 population. The vast majority carried out work both in hospital and in the community, the proportion a reflection of who employed and managed staff. There was a wide variation in the qualifications required and the nursing gradings of DSNs, and regional variation in the number of grade I nurses, with the greatest proportion based in the South-east of England. The vast majority (96%) provided patient education, and where it existed (in 60% of responses), were the major providers of a patient help line (90%). Although key providers of patient education, there had been no specific education for this task in over 20% of responses. There was broad consistency in the topics covered at educational sessions, although advice on footwear (76%) and home urine glucose monitoring (73%) were least frequently documented. The issuing of literature and cards for patient use was also very variable. Over 25% of bids for diabetes service improvement were for additional DSNs, but only 48% of these were successful. CONCLUSIONS: There has been an improvement in staffing levels of DSNs over the last 10 years but the numbers are many fewer than recommended in national strategy documents, with evidence that despite expansion being given a high profile, such efforts are often unsuccessful. There was also evidence of considerable variation in the qualifications and gradings of DSNs throughout the UK and indeed in their day-to-day roles, and the content of patient education programmes. This suggests the need for a nationally co-ordinated approach to training and recruitment.

Association of British Clinical Diabetologists (ABCD): survey of specialist diabetes care services in the UK, 2000. 3. Podiatry services and related foot care issues.

AIM: To examine the provision of, and variations in, podiatry and other services for diabetic foot care in the UK. METHOD: A postal survey of secondary care providers of diabetes services in the UK in 2000. RESULTS: Following two reminders a 77% response rate was achieved. The responses indicated that 97% had a state-registered podiatrist attached to the service, providing three (median) sessions each week for diabetes care, although only 44% had availability at all diabetic clinics, and only 3% had availability at paediatric diabetic services. Podiatry access at all diabetic clinics increased the likelihood of associated preventative as opposed to reactive ('trouble shooting') care (P < 0.05). All individuals with feet at 'high risk' of ulceration had access to 'at least 2 monthly review' in 15% of trusts, and with active foot ulceration at least weekly in 43%. Over 70% used at least one form of equipment to assess peripheral neuropathy, but peripheral blood flow was only formally measured in 13%. Although podiatry input to patient education was common (84%), only 6% had received formal training in education. Guidelines and strategies for management of active foot problems were available in 50-74% of cases. Orthotic input was highly variable, and absent in 15% of responses. Podiatrist fitting and application of foot protective apparatus was only recorded in 22-61% of responses. Access to isotopic and/or MR foot imaging and peripheral angiography and angioplasty was recorded in 75-83% of responses. Separate specialist foot clinics were available in 49%, and where this was the case the use of newer foot ulcer healing applications was higher (P < 0.01). Clear regional differences were apparent in the nature of the service, the use of newer treatments, and in access to an orthotist, a local 'dedicated' foot surgeon or a separate diabetic foot clinic. Of 245 documented bids for service improvements, only 19 related to foot care and only 21% of bids were successful. CONCLUSIONS: Despite an increase in podiatry support to diabetes care over the last 10 years, the level of access and the nature of the services provided is much less than recommended in many advisory documents. The strategy of a co-ordinated 'team' approach to foot care still takes place in less than 50% of centres. There are clear regional differences in diabetes foot care services. Both providers and purchasers of diabetes services may not have given sufficient attention to this area, given the relatively small number of documented bids for service improvements in this area, and the very low success rate of such bids.

Association of British Clinical Diabetologists (ABCD): survey of specialist diabetes care services in the UK, 2000. 4. Dietetic services and nutritional issues.

AIMS: To examine the provision of, and variations in, dietetic services for diabetes in secondary care in the UK. METHOD: A postal survey of all secondary care providers of diabetes services. RESULTS: There was a 77% response rate. A dedicated dietician supported diabetes services in 73% of responses, but only 45% were able to see newly diagnosed patients within 1 month. Only 3% of responses documented that dietetic services provided the recommended minimum 22 h weekly input to diabetes care, and an annual dietetic review was said to be available in 15%. An opportunity for more frequent visits was most likely if there was poor glycaemic control (78% of responses), particularly when services were provided by a dedicated diabetes dietician. Although dieticians frequently provided input to patient education (88%), specific training for this purpose and provision for continuing education of these individuals was less common (14% and 63%, respectively). Nutritional guidelines were available in 74%, but only 31% of responses documented current guidelines on obesity management. Of bids for additional dietetic resources, only 21% had been successful. There was evidence of regional variation in service provision, and no greater provision of dietetic services in areas with a large South Asian population and an expected high prevalence of diabetes. In broad terms, dietetic services for diabetes care had not altered in comparison with a similar survey in 1997. CONCLUSIONS: The level of dietetic support of secondary care diabetes services remains dramatically lower than recommended in advisory documents, and appears to have changed little over the last 3 years. This is compounded by marked regional differences, and was no better in areas with a higher than average prevalence of diabetes. The survey also highlights the need for more co-ordinated and structured education and training of dieticians as well as more consistency in nutritional guidelines.

Association of British Clinical Diabetologists (ABCD) survey of secondary care services for diabetes in the UK, 2000. 1. Methods and major findings.

OBJECTIVE: To examine the provision, and variations in, secondary care diabetes services in the UK. METHODOLOGY AND PARTICIPANTS: A postal survey of all 238 identified secondary care providers of diabetes services in 2000. RESULTS: Following two reminders, a 77% response rate was achieved. Major deficiencies in core staffing levels were recorded, with 36% of services provided by only one consultant physician with an interest in diabetes. The provision of diabetes specialist nurses was less than recommended in 87% of responses, whereas podiatry and dietetic support was unavailable in 3% and 27% of responses, respectively. Diabetes registers were not present in 28%, and a co-ordinated retinopathy screening programme unavailable in 26% of responses. Key biochemical measurements were unavailable in 9% (microalbuminuria) to 18% (HDL-cholesterol) of responses. A 'Well-Resourced Service' score was devised taking account of levels of personnel, facilities and specialized clinical services. There was a significant geographical variation in this score (P < 0.001), with the lowest score (least well-resourced services) in the Eastern NHS Region of England, and the highest score in the North-west NHS Region of England. The 'Well-Resourced Service' score was also significantly lower (P < 0.05) where there were less than two whole-time consultant physicians providing diabetes services. In contrast to other aspects of service provision, availability of dieticians and a combined diabetes-ophthalmology service had declined since 1990. Of 245 recorded bids for resources and service improvements for diabetes care, the success rate overall was 44%, and lowest where bids were made for dietetic and podiatry support. CONCLUSIONS: There is presently a major shortfall in provision of secondary care diabetes services throughout the UK, with evidence that there is significant regional variation and less facilities and resources where there are less than two consultants providing specialized diabetes services. On average bids for service improvements were only successful in < 50% of cases, most usually where the service was relatively better provided for. Considerable development and investment are required nationally to ensure equitable access to specialized diabetes services, a vital component in reducing adverse diabetes outcomes.

Novel bicyclic lactam inhibitors of thrombin: potency and selectivity optimization through P1 residues.

Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl interaction have been prepared. The binding energy lost after the removal of the activated carbonyl was recaptured through a series of modifications of the P1 residues of the bicyclic lactam inhibitors. Selected substituted compounds displayed useful pharmacological profiles both in vitro and in vivo.

Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: transition state inhibitors.

Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic trans-cyclohexylamine P1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model.

In vitro and in vivo properties of bicyclic lactam inhibitors: a novel class of low molecular weight peptidomimetic thrombin inhibitors.

We have developed potent and selective thrombin inhibitors with a novel non-peptidic structure. A bicyclic lactam was used as the scaffold on which various P1 and P3 motifs were substituted. Herein, we report the in vitro and in vivo properties of four representatives of this novel class of inhibitors. Their Ki values were less than 10 nM, they inhibited equally both free and clot-bound thrombin, and they displayed high level of specificity for thrombin over other serine proteases (trypsin, factor Xa, activated Protein C, and plasmin). They prolonged the clotting time of human plasma to twice the control value in coagulation assays (TT, APTT, and PT) at a concentration below 3 microM. Their anticoagulant activities using rat plasma were similar to, although slightly weaker, than with human plasma. Furthermore, they inhibited thrombin-induced platelet aggregation (human and rat) at concentrations close to their Ki values for thrombin. These molecules demonstrated similar dose response antithrombotic efficacy in rat arterial and venous thrombosis models when given as i.v. bolus followed by infusion. Antithrombotic efficacy of 85% and greater was observed at a dose of 5-7 microM/kg/hour in each model. Bicyclic lactam inhibitor 3, at a dose which caused a complete inhibition of visible thrombus formation in the venous and arterial models of thrombosis, showed a 1.9-2.1 and a 4.0-4.8-fold shift in APTT and TT, respectively. Unfortunately, the bicyclic lactam inhibitors exhibited low oral bioavailability in rats. Therefore, this novel class of bicyclic lactam thrombin inhibitor has the potential to be promising intravenous antithrombotic agents for the treatment of arterial as well as venous thrombosis and warrants further investigation.