Diabetic foot problems: prevention and management

Individualised care

Stakeholder feedback indicated a need to further highlight person-centred and personalised lifestyle management advice across the guidelines. The guidelines will be amended with the following standard text placed at the beginning of the recommendations section:

'People have the right to be involved in discussions and make informed decisions about their care, as described in your care.

Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations and has information about prescribing medicines (including off label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.'

Oral health

Stakeholders noted the bi-directional nature of poor oral health and diabetes (that diabetes can cause oral health problems, and conversely, that poor oral health can increase the risk of diabetes). They requested further recommendations on maintaining oral health and treating complications of poor oral health in children with diabetes and adults with type 2 diabetes. The aetiology of diabetes is not within scope for NICE's guidelines on type 1 diabetes in adults, diabetes (type 1 and type 2) in children and young people or type 2 diabetes in adults. However NICE's guideline on diabetes (type 1 and type 2) in children and young people has a cross reference to NICE's guideline on dental recall. Appendix G of the full guideline on dental recall highlights diabetes as a risk factor for developing dental disease and notes that: 'People with diabetes (both type I and type II) are at increased risk of developing destructive periodontal disease and that individuals with diabetes may need a more frequent recall. Inadequate plaque control and the presence of other risk factors will modify the recall interval further'. This issue will be put forward for consideration as part of the scoping for the update of NICE's guidelines on type 1 diabetes in adults and type 2 diabetes in adults as expert input is required to determine an appropriate way of highlighting oral health in people with diabetes.

Insulin therapy for type 1 diabetes

Several stakeholders commented that NICE diagnostics guidance on integrated sensor-augmented pump therapy systems for managing blood glucose levels in type 1 diabetes (the MiniMed Paradigm Veo system and the Vibe and G4 PLATINUM CGM system) is out of date. This guidance is due to be reviewed in 2019 and is not part of the current surveillance review for NICE's guidelines on diabetes. All information provided by stakeholders will be shared with the NICE Diagnostics Assessment Programme.

Diabetic eye screening

We initially proposed to withdraw the recommendations on diabetic eye screening in NICE's guidelines on type 1 diabetes in adults and type 2 diabetes in adults as this is covered by the National Screening Committee. However, stakeholders responded that the guideline still needs to emphasise the importance of regular screening. We will therefore add in a cross reference to the NHS Diabetic Eye screening programme for ease of reference to this guidance.

Real-world data

Several stakeholders requested that observational and real-world data should be used in guideline development and considered as evidence within surveillance reviews. For the purposes of this surveillance review, due to the volume of published evidence on diabetes, only Cochrane review and randomised control trial (RCT) level evidence was included. NICE is however considering how real-world data could be further used, and there will be a public consultation on this, alongside other data analytic considerations, in the summer of 2019.

Diagnosis

Some stakeholders highlighted new evidence to suggest that misclassification of type 1 diabetes may be common in adults diagnosed after the age of 35 years. Further evidence was identified on the use of C-peptide to avoid misclassification of late-onset type 1 diabetes and added to appendix A1 for consideration. They raised concerns that the guideline currently only recommends the use of C-peptide tests if there is clinical uncertainty about diagnosis, particularly as the evidence suggests this could be leading to missed diagnoses. The use of C-peptide tests was an area highlighted by the original guideline committee as needing further evidence, who at the time, made the recommendations based on a consensus agreement. In light of this feedback and the new evidence, we are proposing that this area is reviewed.

Blood glucose monitoring

Many stakeholders called for an update in the area of continuous glucose monitoring (CGM) due to newer trials showing the benefits of it since the guideline was last updated. We initially judged the new evidence to be broadly consistent with the guideline, which currently recommends considering CGM if people have problems with hypoglycaemia. However, following stakeholder concerns and after further consideration of the evidence, which shows a benefit for people with sub-optimal glucose control as well as people with hypoglycaemia, we are now proposing to review this area.

Insulin therapy

Many concerns were raised about the proposal not to add recommendations on closed-loop pump therapies, given the emerging evidence base and other NICE guidance in this area. Further evidence was highlighted which was published after the search cut-off dates for this surveillance review and we have since included it in appendix A1 for consideration. Two ongoing trials were also brought to our attention and have been added to our review. We initially judged the evidence to be insufficient to inform recommendations at this point, noting the lack of studies with long-term outcomes and in patients with sub-optimal diabetes control. The new evidence highlighted by stakeholders has a longer follow-up period and includes people with sub-optimal diabetes control. Following the strong steer from stakeholders and the emerging evidence, we are now proposing to review this area.

Psychological support

Concerns were raised about the recommendations relating to psychological support, with some calling for specific recommendations for people with diabetes (rather than a cross reference to other related guidelines). Currently the guideline contains recommendations on recognition and referral for psychological support, with additional signposting to relevant NICE guidelines which offer more specific advice. We therefore judge this area to be sufficiently covered by existing NICE guidance. As we did not identify any new evidence in this area during the surveillance review, the recommendations will not be changed at this point.

Other areas

Other areas were highlighted for update by individual stakeholders; however, these were not considered to impact the guideline at this point, either due to insufficient evidence or because the issue is covered by existing guidance. These areas included: management of newly diagnosed adults, discussion of diabetic eye screening results, digital photographic and optical coherence tomography surveillance, routine use of autoantibody tests, education, low GI diets, carbohydrate counting, very low calorie diets, blood ketone monitoring, person-centred care, bolus calculators, transition from child to adult services, management of renal complications, diabulimia, immunotherapy and language concerns.

See appendix B1 for full details of stakeholders' comments and our responses.

Patient education

A review of the wording of the patient education recommendations was suggested to emphasise the importance of evidence-based online education. However, the new evidence identified for digital interventions is consistent with the evidenced-based principles set out in the existing guideline recommendations.

Motivational interviewing and mobile phone applications were also proposed for consideration. However, evidence submitted did not meet the surveillance inclusion criteria, and evidence identified in the surveillance review was inconclusive for these interventions.

Dietary advice

Many stakeholders proposed an update of the recommendations on dietary advice. The majority of comments concerned low carbohydrate, low calorie and very low calorie diet interventions. Total diet and meal replacement interventions were also suggested for inclusion. The proposed rationale was the need to move away from the perception of type 2 diabetes as a progressive condition managed with either medicine or insulin, to one that is treatable and reversible through dietary intervention. Stakeholders highlighted the need for people living with type 2 diabetes to receive more information on remission and dietary advice.

Evidence submitted was not eligible due to indirectness of population (relating to obesity without type 2 diabetes, and to prevention not treatment), out of scope study designs, and studies published outside the surveillance search period. The aforementioned joint ADA and EASD guideline was also cited as referring to low carbohydrate and low calorie diets. However, this guideline does not explicitly recommend these diets but states that 'advice should be given of the health benefits of weight loss and encouraged to engage in a programme of intensive lifestyle management, which may include food substitution'. NICE's guideline on type 2 diabetes in adults already advises individualising recommendations for carbohydrate intake, and meal patterns, which could include low carbohydrate and low calorie diets.

Stakeholders also asserted that sufficient evidence was already available on the benefits of these diets to justify recommending them. However, the totality of evidence in this area is limited to short-term benefits of these interventions. It does not indicate that low carbohydrate diets are a superior approach to other strategies for weight loss and subsequent weight maintenance in the long-term. The surveillance impact statement is therefore retained; that the longer-term results of the DIRECT study (beyond 2 years), and other longer-term studies of low calorie and low carbohydrate diets are likely to be needed to establish any definite impact on the guideline. A joint working group of The Scientific Advisory Committee on Nutrition, NHS England and Diabetes UK, with input from the British Dental Association and royal colleges, is reviewing the evidence on low carbohydrate diets with publication expected in 2020. This will be tracked by the surveillance team and the results will be considered when available.

Blood glucose management

The inclusion of real time CGM was proposed, based on the emergence of digital platforms and new clinical evidence. However, the studies submitted could not be included due to study designs being either out of scope or being published outside the surveillance search period. The new RCT evidence identified in the surveillance review supporting the use of CGM for type 2 diabetes is limited by the 6-month duration and no impact on the guideline is anticipated until the findings are substantiated by further longer-term studies.

Drug therapy

Many stakeholders agreed with the surveillance proposal to review the antidiabetic drug pathway with a focus on CVD, renal and other relevant clinical characteristics to ensure consideration of outcomes beyond glycaemia reduction alone. Some supporting studies were submitted and are now included in the evidence summary. Several additional studies were submitted which had already been considered in the evidence review from the 2018 guideline in the areas of SGLT-2 inhibitors and GLP-1 analogues. Other studies were outside the study design scope or search period of the surveillance review. The following specific points were raised, which will inform the proposed review of the antidiabetic drug pathway.

The need to consider drug treatment to prevent renal complications, specifically:

The NICE guideline on type 2 diabetes in adults stipulates a BMI threshold of 35 kg/m² prior to being able to receive a GLP-1 analogue but stakeholder comments suggested that this is not evidence-based. Evidence was submitted by stakeholders to support that GLP-1 analogues consistently reduce HbA1c and body weight regardless of baseline BMI. Although this evidence was not within the scope or search period of the surveillance review it does indicate that the current recommendation may not be accurate. Other inequalities in treatment access and use of healthcare services among ethnic groups was also raised by stakeholders and should be considered in the update of the antidiabetic drug pathway.

The addition of a GLP-1 analogue to a basal insulin was proposed for inclusion as an option for people already on basal insulin who are not also on a GLP-1 analogue. However, the evidence submitted indicating safety and effectiveness was out of scope for the surveillance review. A further point was that, because the majority of diabetes management takes place within primary care, the current recommendation to seek specialist advice when adding a GLP-1 analogue to basal insulin should be removed.

In developing the NICE guideline on type 2 diabetes in adults, the committee agreed that to facilitate a flexible approach to enable access for individuals most likely to benefit, this combination should be available to people for whom obesity is a concern and only where other triple oral combinations are contraindicated or not effective. The guideline committee noted that there was a lack of evidence for combinations of GLP-1 mimetics and insulin, and therefore agreed that this option should only be offered in a specialist care setting. The surveillance review has not identified evidence to warrant a change to this position.

Evidence supporting the use of GLP-1 analogues prior to initiating insulin therapy was submitted, demonstrating similar or greater reductions in HbA1c, greater weight loss and lower rates of hypoglycaemia compared to insulin. This was proposed as an option for patients who need greater glucose lowering benefit prior to insulin, in accordance with the ADA/EASD consensus statement. However, the evidence was not within the scope or search period of the surveillance review.

The DUAL IX study was highlighted, which demonstrated safe use of IDegLira in combination with SGLT-2 inhibitors in insulin naive patients. This study has been included in the surveillance review to inform the update decision.

Stakeholders suggested that the guideline should clearly differentiate between available basal insulins, specifically taking into consideration those people at a higher risk of hypoglycaemia and prioritising a choice of insulin with a lower risk of hypoglycaemia in line with the ADA-EASD guideline. This is consistent with the surveillance review proposal to review this area with consideration of key safety issues.

Managing complications

Stakeholder(s) proposed that specific advice be provided for chronic kidney disease (CKD) as a complication of type 2 diabetes as opposed to the existing cross reference to NICE's guideline on chronic kidney disease in adults. However, CKD and renal outcomes are already proposed for consideration in the review of the antidiabetic drug pathway. More specific advice for CKD in type 2 diabetes will be considered for inclusion in NICE's guideline on chronic kidney disease in adults, which already includes advice for type 1 and 2 diabetes and is cross-linked to from the NICE guideline on type 2 diabetes in adults. A further comment proposed consideration of urinary albumin screening for cardiovascular risk, as opposed to impending end-stage renal disease.

Several points were raised about the surveillance proposal for managing eye disease in type 2 diabetes.

In updating the recommendations for diabetic retinopathy, specialist ophthalmic input was advised. This will be passed on to the developers for consideration in the update.

It was requested that data on the use of fibrates in addition to statins are reviewed in terms of the effects on diabetic retinopathy, based on evidence from Accord and FIELD studies, where fibrates were shown to reduce the rates of progression of retinopathy. However, these studies preceded the surveillance search period and would have been available for consideration when the NICE guideline on type 2 diabetes in adults was developed. No additional evidence in this area was identified through the surveillance review but the NICE surveillance team is monitoring the ongoing Lowering Events in Nonproliferative Diabetic Retinopathy in Scotland study which also concerns fibrate use.

It was highlighted that data is emerging about digital photographic and optical coherence tomography surveillance for certain patients who had already been referred to the diabetic eye clinics ('virtual clinics'). However, no evidence was submitted or identified in the surveillance review, and therefore this area will not be prioritised as part of the update.

Other areas

Comments on several additional areas were submitted without supporting evidence by individual stakeholders. These included: the effect of bariatric surgery on type 2 diabetes, with the resulting remission lasting up to 15 years; concerns that drugs other than aspirin were omitted from the section on antiplatelet therapy, however, recommendation 1.5.2 has a cross reference to NICE's guidelines on cardiovascular disease and myocardial infarction for more detailed advice on antiplatelet therapy for primary and secondary prevention of CVD; the antihypertensive effect of SGLT-2 inhibitor therapy (developers will be made aware of the need to consider antihypertensive benefits of SGLT-2 inhibitors during the proposed review of the antidiabetic drug pathway); liver diseases as comorbidities of type 2 diabetes (there is a separate NICE guideline on non-alcoholic fatty liver disease, which covers NASH, and a cross reference will be added from the NICE guideline on type 2 diabetes in adults to that guideline).

See appendix B2 for full details of stakeholders' comments and our responses.

Diagnosis

A stakeholder raised concerns that the recommendations on diagnosis do not include the use of islet autoantibody testing to distinguish type 1 diabetes from monogenic diabetes. During the development of the NICE guideline, evidence on diagnosis, including the use of islet autoantibody testing was reviewed. Recommendations concerning antibody screening were not made because most of the included studies incorporated an antibody test as part of the gold standard and were not designed as diagnostic test accuracy studies (instead they were prevalence studies). Antibody testing was also described as expensive and not considered cost effective. The guideline development group noted that current practice at the time was to use C-peptide and antibody tests as part of the work-up for diagnosis. However, the evidence included in the guideline review suggested that 'such tests are of no benefit in distinguishing between different types of diabetes and so use of the tests should be discontinued'. The stakeholder provided evidence, but none of the studies were diagnostic accuracy or cost-effectiveness studies, as such this is not currently being considered as an area for update.

The stakeholder also raised concerns that some of the content of recommendation 1.1.6 was incorrect. Specifically, they requested that the recommendation to consider types of diabetes other than types 1 or 2 (such as other insulin resistance syndromes, or monogenic or mitochondrial diabetes) in children and young people with suspected diabetes who have diabetes in the first year of life be changed to 'diabetes in the first 9 months of life'; however the current recommendation does not seem at odds with guidance highlighted by the stakeholder from the International Society for Pediatric and Adolescent Diabetes. The stakeholder also noted that the criterion of rarely or never developing ketone bodies in the blood (ketonaemia) during episodes of hyperglycaemia for considering other types of diabetes than type 1 or type 2 diabetes is incorrect. While rarely or never developing ketonaemia during episodes of hyperglycaemia is rare in people with monogenic or mitochondrial diabetes, this is also the case for children with type 2 diabetes (except in ketosis-prone subtype). We will therefore request that the guideline committee updating the NICE guideline considers how this can be clarified.

Another stakeholder also requested that 'visual disturbance' is added to recommendation 1.1.1 as a characteristic of type 1 diabetes in children and young people. As the evidence referenced is not currently published, we were not able to determine the impact of the study's findings, which has been added as ongoing research to consider once published (see appendix A3).

Insulin therapy for children and young people with type 1 diabetes

Several stakeholders requested that sensor-augmented pump therapy and closed-loop therapy be included as areas for update, however none of the highlighted evidence met the surveillance review inclusion criteria. During the surveillance review only 1 relevant RCT was identified, as such, the evidence base remains limited and further evidence from larger RCTs would be required in order to consider whether this should be an area for update.

Blood glucose monitoring

Seven stakeholders responded that the NICE guideline should be updated in relation to the use of flash glucose monitoring in children with type 1 diabetes. No RCT evidence was provided, but stakeholders reported that it is already being prescribed to some children and young people on the NHS and some guidance indicates that children aged 4 years and older may receive a flash glucose monitor (if other conditions are met). We have therefore decided that NICE should consider the use of this technology in children with type 1 diabetes.

Several stakeholders also responded that real time CGM should be considered as an area for update, alongside the use of technology such as smartphone applications; however the evidence provided by stakeholders had either already been considered within the surveillance review, or did not meet inclusion criteria. The evidence identified in the surveillance review in relation to CGM, including the use of smartphone applications and consideration of the psychological benefits of CGM, supports the content of the current recommendations 1.2.58–1.2.64 and will therefore not be considered as an area for update. Two pieces of relevant ongoing research that were identified by stakeholders will be considered when the results of the studies are published.

One stakeholder also reported that there are issues with the interpretation of 'high levels of physical activity' in recommendation 1.2.63 by clinical commissioning groups determining whether ongoing real‑time CGM should be funded or not. This implementation issue will be addressed by requesting that the guideline committee updating the NICE guideline considers how the recommendation could be amended to provide other examples of 'high levels of physical activity'.

Medications for children with type 2 diabetes

Two stakeholders requested that the update of the NICE guideline looks at the use of insulin in children with type 2 diabetes and the use of GLP-1 receptor agonist liraglutide. Due to the lack of RCT-level evidence exploring the effectiveness of insulin in children with type 2 diabetes, this is not being considered as an area for update at this time. Liraglutide is not currently licensed for use in children, so evidence on this medication is not being considered. If liraglutide is approved for use in children with diabetes, we will look at published RCT evidence of effectiveness in this population at the next surveillance review.

Psychological and social issues in children and young people with type 1 or type 2 diabetes

Several stakeholders raised concerns that some psychological conditions were being prioritised over others, that physical health was prioritised over mental health and that person-centred care needed more emphasis. The NICE guideline covers issues on a wide range of psychological conditions, cross-refers to relevant existing NICE guidelines and highlights the importance of emotional wellbeing and coping in the recommendations sections on psychological and social issues in children and young people with type 1 diabetes and psychological and social issues in children and young people with type 2 diabetes.

Several stakeholders also highlighted that patient-related characteristics and fluctuations in glycaemic control may cause cognitive impairment in children and young people with type 1 diabetes. This is already acknowledged in the NICE guideline. Recommendation 1.2.86 highlights that diabetes teams should consider referring children and young people with type 1 diabetes who have frequent hypoglycaemia and/or recurrent seizures for assessment of cognitive function, particularly if these occur at a young age.

Monitoring for complications and associated conditions of type 2 diabetes

One stakeholder requested that non-alcoholic fatty liver disease (NAFLD) is added as a complication to recommendations 1.3.43–1.3.45 on monitoring for complications and associated conditions of type 2 diabetes. As NICE has an existing guideline on NAFLD which recommends that children and young people with type 2 diabetes are offered a liver ultrasound, we will request an editorial amendment to cross-refer to this guideline in NICE's guideline on diabetes (type 1 and type 2) in children and young people.

Other areas

Comments were also received from single stakeholders in relation to the frequency of eye screening, the definition of hypoglycaemia, the frequency of capillary blood glucose tests per day, treatment of hypoglycemia using fast-acting and long-acting carbohydrates, treating complications of type 1 diabetes, providing more in-depth recommendations on metabolic surgery and on other NICE guidelines. These comments have not resulted in any changes to the surveillance decision due to lack of supporting evidence that meets the inclusion criteria for this surveillance review or applicability to the NICE guideline.

See appendix B3 for full details of stakeholders' comments and our responses.

Wound dressings

Stakeholders raised concerns about recommendation 1.5.10 as they felt that the wording prevented interactive dressings such as UrgoStart being used. No evidence was found at this review that was deemed to impact on the existing recommendation, which allows the most clinically appropriate dressing to be used, including interactive dressings. Additionally, the UrgoStart dressing is covered by NICE's medical technologies guidance on UrgoStart for treating diabetic foot ulcers and leg ulcers, which is linked within the diabetic foot pathway, highlighting the benefits of this dressing to service users.

Amputations

Stakeholders highlighted that minor amputations may be avoidable, in relation to new technologies such as rheophoresis and neuromuscular electronic stimulation. No new evidence was found at this surveillance review relating to these technologies. Studies highlighted by stakeholders did not meet the inclusion criteria for this review. This issue will be noted for consideration at the next surveillance review.

Time to assessment

Increasing time to diagnosis and review times for diabetic foot problems were highlighted by 2 stakeholders. Review times were highlighted in relation to a 2018 audit which found not all new cases of diabetic foot ulcer required an urgent referral. Since consultation on this surveillance review closed, the 2019 version of the audit has published which is in support of the existing recommendations that suggest a rapid referral is made for all new diabetic foot ulcers. No new evidence was found to suggest a change to recommendations, with studies provided by stakeholders not meeting the inclusion criteria for this review.

Peripheral artery disease

Several stakeholders raised issues relating to peripheral artery disease (PAD) including interventions to address ischaemia, lack of evidence around the 10 g monofilament test for diabetic peripheral neuropathy, increase in diagnostic sensitivity when the monofilament test was combined with Neuropad and more information requested on PAD and diabetes. Studies provided by stakeholders in this area did not meet the inclusion criteria for this review. The NICE guideline has several cross references to NICE's guideline on peripheral arterial disease, which were considered sufficient for signposting service users to there for further information.

Antimicrobial prescribing guideline (APG)

An APG is in progress for diabetic foot infection which also had a consultation period at the same time as this guideline. The APG will replace recommendations 1.6.6–1.6.15. Through the consultation for the APG, a number of stakeholder comments were raised that are relevant to the other areas of the NICE guideline. A number of these are areas that have already been considered as part of this surveillance review. Comments were raised about terminology such as including more emphasis for the clinical urgency of Charcot arthropathy and more detailed definitions for ischaemia. As no new evidence was put forward during consultation, we will log these issues and consider them again at the next surveillance review. Several stakeholders highlighted a reliance on the results of wound swabs for changing antibiotics and noted that these results may not always be representative of the causative organism. We are tracking a NIHR trial which compares wound swab diagnosis to that of tissue sampling which we hope will provide new evidence in this area. When the results are available, we will assess them against the current guideline recommendations.

See appendix B4 for full details of stakeholders' comments and our responses.

See ensuring that published guidelines are current and accurate in developing NICE guidelines: the manual for more details on our consultation processes.