Professor Stephanie Amiel reviews the updated NICE guideline on type 1 diabetes in adults, focusing on changes to the guidance, particularly those that affect current practice
Read this article to learn more about:
- the importance of primary care services for good diabetic control
- updated recommendations on the use of basal and meal-related insulin
- how to help patients self-manage their diabetes through blood glucose monitoring and insulin dose adjustment.
After reading this article, ‘ Test and reflect ’ on your updated knowledge with our multiple-choice questions. We estimate that this activity will take you 30 minutes—worth 0.5 CPD credits.
Type 1 diabetes is an autoimmune condition in which the body destroys the pancreatic beta cells that normally make the insulin that controls metabolism in response to the glucose available to them. About one half of cases develop in adulthood,1 and many more adults in the UK have the condition than children.2 Type 1 diabetes accounts for about 10% of the UK's cases of diabetes, with more than 300,000 people having the disease.2
From the start of type 1 diabetes, insulin deficiency in people with the condition is much more severe than in those with type 2 diabetes. Individuals with type 1 diabetes are therefore much more dependent on getting insulin doses exactly right to prevent hyperglycaemia, which, over time, is associated with: vascular damage3 and, acutely, ketoacidosis,4 a potentially fatal outcome of insulin deficiency; and hypoglycaemia, which can result in confusion, coma, or seizures5 if concentrations of glucose in plasma fall below those needed for normal brain function. Hypoglycaemia can also precipitate cardiac arrhythmia and is thought to account for 4–10% of deaths in people with type 1 diabetes.6
Although type 1 and type 2 diabetes are very different diseases, they share an increased risk of vascular complications. Microvascular complications, which damage the optic retinae, kidneys, and nerves, are specific to diabetes. Macrovascular complications, which cause heart attacks, strokes, and peripheral vascular disease, are not specific to diabetes, but they occur earlier and more extensively than in people without diabetes.7 The complications of diabetes, and the disabilities resulting from them, are preventable, as tight glycaemic control significantly reduces the risk of microvasular and macrovascular disease,8,9 reducing premature mortality.10 No data suggest that other strategies to protect against vascular damage, such as blood-pressure control and lipid lowering, are less valuable than in people without diabetes. Regular inspection for early complications, allowing timely intervention to prevent disability, is key to good management.
Awareness of the potential psychological impact of living with type 1 diabetes is also important; the healthcare professionals providing care can detect and offer early management for issues such as non-severe anxiety and depression.
NICE Guideline 17
NICE Guideline 17 (NG17) on Type 1 diabetes in adults: diagnosis and management (see Boxes 1 and 2, below), published in August 2015, is an update of Clinical Guideline 15 (CG15) from 2004.11,12 The update was timely because life expectancy in patients with type 1 diabetes is still reduced by 11–13 years (cardiovascular death is the most common cause),13 targets for diabetes control are not being met,14 and people are still presenting with and dying from diabetic ketoacidosis.15 Furthermore, advances have been made in our knowledge and in the technologies available for insulin replacement and glucose monitoring. The NG17 update reviewed the latest evidence to determine how new therapies can be used best to achieve better outcomes.11 This article focuses on recommendations that are new for 2015 (see Box 3, below), particularly those that should change current practice.
Box 1: NICE Accreditation Mark
NICE Guideline 17 on Type 1 diabetes in adults: diagnosis and management has been awarded the NICE Accreditation Mark.
Box 2: NICE Pathways
This NICE guidance is part of the NICE Type 1 diabetes in adults pathway, available at: pathways.nice.org.uk/pathways/diabetes
Box 3: Updated and new topics included in NICE NG17 on Type 1 diabetes in adults: diagnosis and management11
Topics updated in NG17 (i.e. topics that have been revised from CG15)
- diagnosing type 1 diabetes
- structured education programmes
- insulin preparations and regimens associated with improved glucose levels
- needle length for insulin injections
- new technologies for glucose monitoring and insulin delivery
- managing acute painful neuropathy associated with rapid blood glucose control, erectile dysfunction in men, and gastroparesis
- primary prevention of cardiovascular disease.
New topics included in NG17 (i.e. topics added that were not part of CG15):
- new insulin formulations
- identifying, quantifying and managing impaired awareness of hypoglycaemia
- monitoring for thyroid disease
- use of blood ketone measurement in preventing and monitoring diabetic ketoacidosis
- carbohydrate counting and glycaemic index diets
- referral criteria for transplantation therapies.
Adapted from: NICE (2015) NG17. Type 1 diabetes in adults: diagnosis and management. NICE, 2015. Available at: www.nice.org.uk/ng17
Reproduced with permission
Delivery of care
Most adults with type 1 diabetes (like all children) receive at least some care from specialist services. About 20% attend primary care exclusively, and primary care teams will increasingly be involved in delivering aspects of care such as monitoring and management of secondary complications. Indeed, general practitioners are front-line in the diagnosis of type 1 diabetes and acute decompensation of metabolic control.
The 2015 NICE update on management of type 1 diabetes in adults (NG17) reiterates the need for open-access services during working hours and a 24-hour helpline staffed by people with specific expertise in diabetes.11 Although the relative rarity of type 1 diabetes and the complexity of modern insulin management require specialist support, this must be coordinated and organised in collaboration with services in primary care and should increasingly be provided in venues and formats most convenient to the user.
Diagnosis of type 1 diabetes
Diagnosis of type 1 diabetes is still based on clinical presentation. The hallmarks of type 1 diabetes in someone presenting with hyperglycaemia are ketosis, rapid weight loss, age <50 years, body mass index (BMI) <25 kg/m2, and a personal or family history of autoimmune disease; however, the diagnosis should not be discounted in adults with higher BMIs or older age at presentation.11 The presence of moderate or high levels of ketonuria—or blood ketone value >3 mmol/l—indicates the need for immediate treatment and emergency referral to hospital for parenteral rehydration and insulin initiation if the patient is clinically unwell and/or vomiting.11 Testing for markers of autoimmunity and residual insulin secretion is reserved for people with atypical features and those in whom the classification of diabetes is uncertain, who may require specialist review. Meanwhile, the possibility that other autoimmune conditions may arise in adults with type 1 diabetes should be considered whenever clinically indicated, with routine measurement of thyroid-stimulating hormone (TSH) as part of the annual review.11
Education and information for adults with type 1 diabetes
The person who has diabetes has to provide their own day-to-day care, and proper training in how to manage their condition is essential. Care planning should start immediately after diagnosis pending resolution of any medical emergency. NICE NG17 lists the topics to be covered at this time (see Box 4, below) and mandates annual review of a patient's knowledge and the need for ongoing educational input.11 Relevant education should be offered at every clinical encounter. Insulin replacement is logical but complex, and the best results are achieved by the person with diabetes engaging with management and adjusting doses on a daily basis to support a flexible lifestyle.16
Box 4: Elements of an individualised and culturally appropriate early care plan11
Elements of an individualised and culturally appropriate plan will include:
- sites and timescales of diabetes education, including nutritional advice
- initial treatment modalities, including guidance on insulin injection and insulin regimens
- means of self-monitoring and targets
- symptoms, risk and treatment of hypoglycaemia
- management of special situations, such as driving
- means and frequency of communication with the diabetes professional team
- management of cardiovascular risk factors
- for women of childbearing potential, implications for pregnancy and family planning advice (see the NICE guideline on diabetes in pregnancy)
- frequency and content of follow-up consultations, including review of HbA1c levels and experience of hypoglycaemia, and annual review.
NICE (2015) NG17. Type 1 diabetes in adults: diagnosis and management. NICE, 2015. Available at: www.nice.org.uk/ng17
Reproduced with permission
All adults with type 1 diabetes should receive structured education on flexible self-management of insulin through a programme 'of proven benefit' that is evidence-based, curriculum driven, delivered by trained educators, quality controlled, and regularly audited. NICE NG17 recommends the dose adjustment for normal eating (DAFNE) programme as an exemplar.11,17 This should be offered 6–12 months after diagnosis,11 when the 'honeymoon period' of some recovery of insulin secretory function that occurs after immediate treatment is over, or at any other time when it is clinically appropriate.
The DAFNE programme—and programmes like it—are designed to transfer the skills of insulin dose adjustment from healthcare professional to patient.17 The courses teach people to assess the carbohydrate content of the foods they wish to eat and to adjust their pre-meal insulin dose based on that, the glucose measured just before the meal, the results of previous blood glucose monitoring, and the expected impact of planned or recent activity.18 It sounds a lot for a patient to consider, but focusing attention on the diabetes for a few minutes before each insulin injection means that the patient can have confidence in the dose selected and worry less about its consequences until the next insulin dose is due.19 Patients educated through good programmes such as these benefit from: better overall glucose control; fewer episodes of hypoglycaemia and diabetic ketoacidosis; less depression and anxiety; and better quality of life.20 -22 It is essential to make the patient aware that education is an integral part of diabetes care—not an optional extra!
Type 1 diabetes results from insulin deficiency, so the mainstay of treatment is insulin replacement rather than diet. Nevertheless, dietary manipulation is an important aid to achieving treatment targets. In addition to learning how to estimate the carbohydrate content of food to be eaten (ideally as part of a structured education programme that covers all aspects of insulin dose self-adjustment, as described above), adults with type 1 diabetes should be shown how to use diet—and physical activity—to optimise their cardiovascular health. Evidence does not support the use of low glycaemic index diets for control of blood glucose in adults with type 1 diabetes.11 For sources of further information for patients, see Box 5, below.
Box 5: Sources of further information
Diet and carbohydrate counting
Blood glucose management
Each person's glycaemic control should be monitored through measurement of glycated haemoglobin (HbA1c) every 3–6 months—occasionally more often if glucose control is changing rapidly. The result must be available during consultations. NICE NG17 states that services should: 'Support adults with type 1 diabetes to aim for a target HbA1c of 48 mmol/mol (6.5%) or lower, to minimise the risk of long-term vascular complications.'11 This empowers adults with type 1 diabetes to access the support they need to achieve optimum outcomes. However, not everyone can—or needs to—score a bull's eye to win. The average HbA1c achieved by groups of people is always higher than the target for which they are aiming. The HbA1c target in the landmark Diabetes Control and Complications Trial was 6.05% (43 mmol/mol), but the mean achieved during intensive treatment, with all of its long-term benefits, was around 7.3% (56 mmol/mol).8 With the 2004 target from NICE CG15 of ≤7.5% (59 mmol/mol),12 the national average was 8.7% (72 mmol/mol).14 NICE NG17 requires services to audit their outcomes to report the percentage of patients who achieve 7% (≤53 mmol/mol).11 However, it is very important that the target HbA1c is achieved without problematic hypoglycaemia, and so each patient needs an individualised target, and those with advanced complications or limited life expectancy may require a higher target if prevention of long-term complications is less relevant to them.11 However, healthcare professionals should be aware that programmes such as DAFNE result in reductions in both HbA1c and the rate of hypoglycaemia.17
Self-monitoring of blood glucose
Adults with type 1 diabetes need to be taught how to self-monitor their blood glucose levels and how to use the results, with annual review of their training needs. The fingertips should be used for testing. Patients should be advised to monitor at least four times a day—before meals and before bed—and should be supported to measure up to 10 times a day if there are problems achieving target HbA1c or avoiding hypoglycaemia or when other reasons necessitate more frequent testing. Plasma glucose targets are in keeping with the HbA1c target: 4–7 mmol/l before meals (except before breakfast, when 5–7 mmol/l is associated with fewer episodes of nocturnal hypoglycaemia). Patients who choose to test after meals should do so no fewer than 90 minutes after eating, with a target of 5–9 mmol/l.11 The bedtime target is set according to when the last meal was eaten.11 As with HbA1c, values outside—or even occasionally off—the target are not a disaster but may be an indication to make dose adjustments at the time or prospectively to subsequent doses.
Continuous glucose monitoring (CGM) devices comprise a small electrode that the patient places in subcutaneous tissue to provide a real-time readout calibrated to the finger-prick plasma glucose level.
There is a time delay inherent in their operation, and when plasma glucose is changing rapidly—e.g. after eating—the monitor reading will not be the same as the finger-prick glucose level. Nevertheless, CGM shows the direction of change of blood glucose and correlates well when stable. Some devices connect to insulin pumps that deliver insulin as a continuous infusion, which may be suspended automatically when hypoglycaemia is detected or predicted. After a review of the evidence on efficacy and cost effectiveness, NG17 does not recommend CGM for routine use; however, it should be considered for people with problematic hypoglycaemia despite multiple daily injections and conventional monitoring.11 NICE is currently developing diagnostics guidance on integrated sensor-augmented pump therapy systems for managing blood glucose levels, which is due out in January 2016.
The insulin regimen of choice for adults with type 1 diabetes is multiple daily injections, with basal insulin (to control the body's own glucose production) replaced separately from meal-related insulin.11
NICE NG17 recommends using insulin detemir twice daily (morning and bedtime) as the basal insulin, adjusting the dose based on blood tests fasting before breakfast, or before the evening meal, having not taken carbohydrate or fast-acting insulin at lunchtime.11,20 A network meta-analysis ranked this regimen first in terms of the level of HbA1c achieved and the risk of hypoglycaemia, as well as cost effectiveness.23 Other evidence indicates that twice-daily basal insulin provides superior diabetes control over once-daily basal insulin, possibly because of the greater potential flexibility of dosing (e.g. to accommodate diurnal rhythms or variations in exercise or alcohol intake).24 Other regimens—for example, one that is already working for the patient or once-daily insulin glargine or detemir if the patient rejects the twice-daily regimen—are second choices. Other insulins should be used only if the recommended regimens do not achieve target levels.11
Meal-related control should involve a fast-acting analogue insulin—rather than human- or animal-derived insulin—injected before meals to control the postprandial increase in glucose levels.11 Meal doses, often described in ratios of units of insulin to grams of carbohydrate to be eaten, can be adjusted at the time of administration on the basis of the pre-meal blood test (adding a correction dose if the glucose is over target) and prospectively on the basis of how well the current doses performed on previous days.17 Patient choice should be considered when selecting a meal-related insulin, as it is how the insulins are used that is likely to be important rather than the exact product.
The first-line regimen described above should be offered from diagnosis. Failure to achieve targets despite best efforts with the recommended regimen may justify consideration of insulin pump therapy, as outlined in NICE Technology Appraisal 151 on Continuous subcutaneous insulin infusion for the treatment of diabetes mellitus.25 NICE NG17 recommends consideration of the following factors when a person's glucose control is erratic and seems to be unpredictable:11
- injection technique
- injection sites
- self-monitoring skills
- knowledge and self-management skills
- nature of lifestyle
- psychological and psychosocial difficulties
- possible organic causes such as gastroparesis.
Hypoglycaemia (low level of blood glucose) is patient's most feared complication of insulin therapy.26 People with renal impairment and other comorbidities are at increased risk of severe episodes27 (those in which the person is rendered incapable of self-treatment and/or accompanied by coma or seizure), as are all patients who have impaired awareness of minor hypoglycaemic episodes.28 Each person's awareness of hypoglycaemia should be assessed at least annually—for example, with the 'Gold score', in which the patient ranks awareness ('Do you know when hypos are starting?') from 1 (always aware) to 7 (never aware).11 A score ≥4 indicates impaired awareness and a high risk of severe hypoglycaemia.29 The patient's relatives can reveal a problem of which the patient is not aware. Impaired awareness is sustained by recurrent exposure to plasma glucose levels <3 mmol/l. Awareness can be regained—without loss of control of HbA1c —by: avoiding recurrent exposure to plasma glucose levels <3 mmol/l; sequential use of structured education, use of technologies such as pumps and sensors,30 and even, for a few patients, replacement of defective beta cells by transplantation.31 Simply aiming for higher targets is not helpful. Some patients may feel that hypoglycaemia is the price they pay to avoid hyperglycaemia, but this is not a necessary association and targets below those recommended should be discouraged. Referral for specialist input should be offered in a timely manner.
Some of the targets in NICE NG17 may seem aspirational, but these are the aspirations of our patients. Provision of structured education for all adults with type 1 diabetes is not an option we can fail to deliver, but service reorganisation will be needed, as well as greater flexibility in how the education is delivered, as the proportion of adults with type 1 diabetes currently receiving structured education every year is low. Collaboration between generalist care and specialist teams is needed to ensure that all adults with type 1 diabetes can access the help they need to achieve their targets and good outcomes in the areas that matter to them.
The revised guideline focuses exclusively on adults with type 1 diabetes, recognising the unique needs of this group of people. It reinforces many of the recommendations made in 2004 but updates them based on the availability of new treatment modalities and new knowledge.
Perhaps the biggest challenges in the revised guideline are the heightened expectation of being able to achieve better control than previously considered necessary or possible, the reinforced focus on detecting and avoiding problematic hypoglycaemia, and greater clarity around the cost effectiveness of specific insulin regimens and more intensive self-monitoring. Successful implementation of these recommendations may require some re-focusing of current service provision, to allow every adult with type 1 diabetes access to the structured education programmes and, where necessary, the technological advances, that can deliver better outcomes.
Primary care has a major role to play in ensuring that adults with type 1 diabetes understand the need for these and have access to the support they require to benefit from what they can offer
The author would like to thank the members of the Guideline Development Group for their work in producing the updated guideline. Details of those involved can be found at: www.nice.org.uk/ng17
After reading this article, ‘ Test and reflect ’ on your updated knowledge with our multiple-choice questions. We estimate that this activity will take you 30 minutes—worth 0.5 CPD credits.
NICE implementation tools
NICE has developed the following tools to support implementation of NICE Guideline 17 on Type 1 diabetes in adults: diagnosis and management:
- baseline assessment tool
- costing statement
- costing template.
The tools are available to download from: www.nice.org.uk/guidance/ng17/resources
An online teaching tool is also available at: elearning.nice.org.uk
- Type 1 diabetes is a disease of insulin deficiency, for which the treatment is insulin replacement
- Ketosis and ketoacidosis are hallmarks of the insulin deficiency of type 1 diabetes
- Adults with type 1 diabetes—and their healthcare professionals—need to recognise that attendance at accredited structured education in flexible insulin therapy, transferring skills of insulin dose adjustment from healthcare professional to patient, is an integral part of treatment and should start from diagnosis
- Adults with type 1 diabetes should be supported to aim for a target HbA1c level of 48 mmol/mol (6.5%) or lower, to minimise the risk of long-term vascular complications
- An individualised target should be set for each patient and it must be achieved without problematic hypoglycaemia
- HbA1c should be measured routinely at 3–6 monthly intervals, and the result should be available to the healthcare professional and the patient at consultation
- The insulin regimen of choice for adults with type 1 diabetes includes twice-daily insulin detemir as basal replacement and a fast-acting analogue injected before eating
- Adults with type 1 diabetes should perform self-monitoring of plasma glucose between four and ten times a day
- The annual review should include an assessment of the patient's educational needs and self-monitoring skills, as well as of diabetes control and complication status and a thyroid-stimulating hormone check
- Risk for severe hypoglycaemia and hypoglycaemia awareness should be assessed at least annually, with consideration for early referral to specialist care if the patient is experiencing severe hypoglycaemia or complete unawareness.
HbA1c =glycated haemoglobin
GP commissioning messages
written by Dr David Jenner, NHS Alliance GMS contract/PBC Lead
- NICE Guideline 17 sets tight targets for glycaemic control that will require the provision of intensive education programmes and multiprofessional support to achieve
- Each patient should have a personalised care plan for their care which should stipulate who has the responsibility for undertaking annual review of care, hypoglycaemic awareness, and ongoing education
- Commissioners should:
- ensure 24/7 support is available to patients and attending healthcare professionals via dedicated telephone helplines to diabetes experts
- agree with local primary care and secondary care providers how this is captured in a patient-held record to aid coordination between services
- Commissioners and local specialist diabetes providers should consider regular education events for frontline healthcare professionals, who are increasingly at risk of becoming de-skilled in the management of type I diabetes but who hold a vital role in dealing with emergencies and co-existing problems
- Commissioners could audit primary care databases for glycaemic control in people with type 1 diabetes and target intensive support to those with poor control, who often do not readily engage with health services.
Read the Guidelines summary of NG17 on Type 1 diabetes in adults: diagnosis and management for more recommendations on handling type 1 diabetes in primary care
- Australian Institute of Health and Welfare. Analysis of national diabetes register. Available at: www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129546992 (accessed 22 December 2015).
- Diabetes UK. Diabetes facts and stats. Version 4. London: Diabetes UK, 2015. Available at: www.diabetes.org.uk/Documents/Position%20statements/Facts%20and%20stats%20June%202015.pdf (accessed 22 December 2015)
- Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care 1978; 1: 252–263.
- Daneman D. Type 1 diabetes. The Lancet 2006; 367 (9513): 847–858.
- MacLeod K, Hepburn D, Frier B. Frequency and morbidity of severe hypoglycaemia in insulin-treated diabetic patients. Diabet Med 1993; 10 (3): 238–245.
- Cryer P. Severe hypoglycemia predicts mortality in diabetes. Diabetes Care 2012; 35: 1814–1816.
- Health and Social Care Information Centre. National diabetes audit, 2011–2012. Report 2: complications and mortality. Leeds, HSCIC, 2013. Available at: www.hscic.gov.uk/catalogue/PUB12738/nati-diab-audi-11-12mort-comp-rep.pdf
- Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–986.
- Nathan D, Cleary P, Backlund J et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353: 2643–2653.
- Orchard T, Nathan D, Zinman et al. Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA 2015; 313: 45–53.
- NICE. Type 1 diabetes in adults: diagnosis and management. NICE Guideline 17. London: NICE, 2015. Available at: www.nice.org.uk/guidance/ng17 (accessed 22 December 2015).
- NICE. Diagnosis and management of type 1 diabetes in children, young people and adults. Clinical Guideline 15. London: NICE, 2004. Available at: www.nice.org.uk/guidance/cg15 (accessed 22 December 2015)
- Livingstone S, Levin D, Looker H et al. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA 2015; 313: 37–44.
- Health and Social Care Information Centre. National diabetes audit, 2012–2013. Report 1: care processes and targets. Leeds: HSCIC, 2013. Available at: www.hscic.gov.uk/catalogue/PUB12421/nati-diab-audi-11-12care-proc-rep.pdf. (accessed 22 December 2015)
- Hockenhull J, Dhillo W, Andrews R, Paterson S. Investigation of markers to indicate and distinguish death due to alcoholic ketoacidosis, diabetic ketoacidosis and hyperosmolar hyperglycemic state using post-mortem samples. Forensic Sci Int 2012; 214 (1–3): 142–147.
- National Clinical Guideline Centre. Type 1 diabetes in adults: diagnosis and management. Methods, evidence and recommendations. Clinical Guideline NG17. NICE, 2015. Available at: www.nice.org.uk/guidance/ng17/evidence/full-guideline-435400241
- DAFNE website. www.dafneonline.co.uk (accessed 14 Jan 2016).
- Lawton J, Rankin D, Cooke D et al. Patients experiences of adjusting insulin doses when implementing flexible intensive insulin therapy: a longitudinal, qualitative investigation. UK NIHR DAFNE Study Group. Diabetes Res Clin Pract 2012; 98: 236–242
- Rankin D, Cooke D, Clark M et al; UK NIHR DAFNE Study Group. How and why do patients with Type 1 diabetes sustain their use of flexible intensive insulin therapy? A qualitative longitudinal investigation of patients self-management practices following attendance at a Dose Adjustment for Normal Eating (DAFNE) course. Diabet Med 2011; 28 (5): 532–538.
- DAFNE Study Group. Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes: dose adjustment for normal eating (DAFNE) randomised controlled trial. BMJ 2002; 325 (7367): 746.
- Hopkins D, Lawrence I, Mansell P et al. Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE experience. Diabetes Care 2012; 35: 1638–1642.
- Elliott J, Jacques R, Kruger J et al. Substantial reductions in the number of diabetic ketoacidosis and severe hypoglycaemia episodes requiring emergency treatment lead to reduced costs after structured education in adults with type 1 diabetes. Diabet Med 2014; 31: 847–853.
- Dawoud D, Fenu E, Wonderling D et al. Basal insulin regimens: systematic review, network meta-analysis, and cost-utility analysis for the National Institute for Health and Care Excellence (NICE) Clinical Guideline on type 1 diabetes mellitus in adults. Value Health 2015; 18: A339.
- Hopkinson H, Jacques R, Gardner K et al. Twice- rather than once-daily basal insulin is associated with better glycaemic control in type 1 diabetes mellitus 12 months after skills-based structured education in insulin self-management. Diabet Med 2015; 32: 1071–1076.
- NICE. Continuous subcutaneous insulin infusion for the treatment of diabetes mellitus. Technology Appraisal 151. London: NICE, 2008. Available at: www.nice.org.uk/guidance/ta151 (accessed 22 December 2015).
- Stuckey H, Mullan-Jensen C, Reach G et al. Personal accounts of the negative and adaptive psychosocial experiences of people with diabetes in the second Diabetes Attitudes, Wishes and Needs (DAWN2) study. Diabetes Care 2014; 37: 2466–2474.
- Alsahli M, Gerich J. Hypoglycemia, chronic kidney disease, and diabetes mellitus. Mayo Clin Proc 2014; 89: 1564–1571
- Seaquist E, Anderson J, Childs B et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013; 36: 1384–1395.
- Gold A, MacLeod K, Frier B. Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care 1994; 17: 697–703
- Yeoh E, Choudhary P, Nwokolo M et al. Interventions that restore awareness of hypoglycemia in adults with type 1 diabetes: a systematic review and meta-analysis. Diabetes Care 2015; 38: 1592–1609.
- Choudhary P, Rickels M, Senior P et al. Evidence-informed clinical practice recommendations for treatment of type 1 diabetes complicated by problematic hypoglycemia. Diabetes Care 2015; 38: 1016–1029. G