Life expectancy in the 370,000 people with type 1 diabetes mellitus (T1DM) in the UK remains lower than those without diabetes. The delivery of care is variable, with a substantial north-south divide in England for major lower limb amputations1. The easily avoidable complication of diabetic ketoacidosis is on the rise, as is renal impairment and amputation, despite a decrease in referable blindness2. The immediate and long-term costs of long-term complications are substantial, with amputation, for example, costing an estimated £9,546.3
NICE guidance NG17, published in August 2015, provides evidence-based, practical advice on the diagnosis and management of T1DM in adults. Much has changed, particularly in relation to the provision of education, self-monitoring of glucose and insulin therapy.
Diagnosis and early care plan
The diagnosis of T1DM is primarily made on clinical grounds, when an individual presents with:
- Weight loss
- Age below 50 years
- BMI <25 and="" li="">
- A personal or family history of autoimmune disease
The routine measurement of C-peptide and diabetes-specific autoantibodies is discouraged. However, these should be undertaken when the clinical picture is not so clear, for example, when the patient is >50 years of age or has a BMI >25, when there is a clinical suspicion of monogenic diabetes, or when confirmation of T1DM will enable funding for continuous subcutaneous insulin infusion (CSII). The professional team needs to develop an early care plan based on a formal medical assessment to secure the diagnosis, ensure appropriate acute care in the context of the individual’s social, home and work circumstances, and implement a tailored diabetes education programme and treatment modalities.
Support and individualised care
Individualised advice should be provided in a co-ordinated manner by a range of professionals with skills in the management of diabetes. An individual care plan should be agreed jointly, and reviewed and modified annually in relation to nutrition, self-monitoring, insulin dose adjustment, avoiding hypoglycaemia and achieving optimal glycaemic control to prevent long-term complications.
Education and information
NICE now recommends that all adults with T1DM should be offered a structured education programme such as DAFNE (dose-adjustment for normal eating) within 12 months of diagnosis, and the outcomes should be audited regularly.
The impact of DAFNE on HbA1c is at best moderate, with a fall in HbA1c from 9.1% to 8.8% over 12 months. However, studies have shown significant improvement in quality of life4 and a 61% reduction in the risk of ketoacidosis, with emergency treatment costs for ketoacidosis and severe hypoglycaemia reduced by 64%5. For individuals with recurrent hypoglycaemia, a new recommendation is to offer the Blood Glucose Awareness Training (BGAT) programme.
Carbohydrate-counting training should be offered to all adults with T1DM as part of a structured education programme, but a low glycaemic index diet should not be advised. Dietary advice should be provided by trained professionals, who can advise on insulin dose adjustment relative to carbohydrate and other food intake, taking into account acute glucose excursions as well as long-term benefits on vascular health.
Healthcare professionals should provide advice on the most appropriate intensity and frequency of physical activity as a part of a healthier lifestyle, by emphasising the role of self-monitoring and change in insulin or nutritional intake during and after exercise.
Blood glucose management
HbA1c should be measured every three to six months and more often in those where control is changing rapidly. The result should be available at the time of consultation and ideally, it should have been measured recently to enable individualised, immediate advice.
When HbA1c is invalid (for example, because of disturbed erythrocyte turnover), fructosamine estimation, quality controlled blood glucose profiles and total glycated Hb estimation (abnormal Hb) should be deployed.
NICE recommends a target HbA1c of 48mmol/mol (6.5%) or lower, but advises that this should be individualised to avoid problematic hypoglycaemia. Diabetes services should document the proportion of adults with T1DM achieving an HbA1c of 53mmol/mol (7%) or lower. Routine blood glucose testing at least four times a day, before each meal and before bed is advocated. This can be increased to 10 times a day where a desired HbA1c is not being achieved, where there is frequent hypoglycaemia, or if there is a legal requirement (such as before driving), during illness, before and after sport or during pregnancy.
Target plasma glucose levels comprise the following:
- On waking: 5-7 mmol/L
- Before meals: 4-7 mmol/L
- 90 minutes after eating: 5-9 mmol/L
Increased self-monitoring should be optimised through structured education programmes. Continuous glucose monitoring systems (CGMS) have garnered much interest recently, with the introduction of several new devices.6 They can give both real time and glucose trend data, providing not only point-of-care testing, but also warning trends for rising or falling blood sugars. Taking paracetamol can artificially raise CGM values by about 3-4mmol/L within 60 minutes of ingestion and they can remain elevated for at least four hours.7 Routine use of CGMS is not advocated, but instead they should be targeted in individuals who:
- Are willing to commit to use CGMS at least 70% of the time
- Have complete loss of awareness of hypoglycaemia
- Have more than two episodes of hypoglycaemia per week
- Have an HbA1c >9% despite testing 10 times a day
- Can sustain HbA1c <7% or have achieved a fall of >2.5% with CGMS
CSII has been shown to be cost-effective compared with multiple daily insulin injections (MDI) in patients with T1DM and poor glycaemic control and/or problematic hypoglycaemia.8 CSII improves objective measures of neuropathy compared with MDI, despite a comparable HbA1c over two years.9
There is no place for twice-daily mixed insulin regimens for subjects with T1DM. All subjects should be offered multiple daily injection basal-bolus insulin regimens (this is a new recommendation).
Twice-daily insulin detemir is the preferred choice for basal insulin therapy, with alternatives such as once-daily insulin glargine or detemir if twice-daily detemir is not acceptable.
Any rapid-acting insulin analogue, rather than rapid-acting soluble human or animal insulin, should be used before, not after a meal. For patients with erratic and unpredictable blood glucose, consider:
- Injection technique and site, especially lipohypertrophy
- Knowledge and self-management skills
- Psychological and psychosocial difficulties
If a patient has a BMI of 25 (23 for people from South Asian and related minority ethnic groups), consider adding metformin to improve blood glucose control.
Insulin injection delivery devices, in the form of one or more types of pen or alternative injection devices with different lengths of needles, should be offered to all patients with T1DM. Needle-free systems should be offered to those with a fear of needles.
Injection sites should be checked at least annually, or if new problems arise with hypoglycaemia or unpredictable glucose control. CSII provides rapid-acting insulin at an adjustable rate and is NICE approved (CG151) for children >12 years and adults. Despite compelling data supporting the cost-effectiveness of CSII in relation to improved life expectancy and quality-adjusted life expectancy, driven by lower HbA1c and frequency of hypoglycaemia,8 it remains underused in the UK.
Islet or pancreas transplantation
Simultaneous pancreas and kidney transplantation (SPK) may be an option for patients with T1DM and endstage renal failure. Pancreatic islet cell transplantation is approved by NICE and funded by the National Commissioning Group for patients with severe recurrent hypoglycaemic episodes. Research has shown an improvement in neuropathy in patients undergoing SPK.10,11 The primary referral criterion for islet and/or pancreas transplantation is that of recurrent severe hypoglycaemia that has not responded to other treatments, such as CSII.
Awareness and management of hypoglycaemia
Awareness of hypoglycaemia should be quantified annually using the Gold or Clarke scores. All individuals with impaired awareness of hypoglycaemia should have structured education and additional education focusing on avoiding and treating it. A fast-acting oral form of glucose is needed to manage hypoglycaemia and if there is a decreased level of consciousness, IM glucagon should be administered by friends or family.
Ketone monitoring (blood or urine) should be considered as part of ‘sick-day rules’ for patients so they can self-manage episodes of hyperglycaemia. Capillary ketone testing should be undertaken for adults presenting to the emergency services with suspected DKA or uncontrolled diabetes with a period of illness.
Associated illness and thyroid disease
Given the coexistence of other autoimmune diseases in patients with T1DM, healthcare professionals should be alert to the development of Addison’s disease and pernicious anaemia and in those with a low BMI or unexplained weight loss, coeliac disease. Thyroid-stimulating hormone levels should be measured at annual review.
Cardiovascular risk reduction
Aspirin should not be offered for the primary prevention of cardiovascular disease in T1DM. All patients with T1DM should undergo an annual assessment of cardiovascular risk. Lipid profile (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) should be assessed at least once (this can be a non-fasting sample). The profile should be repeated three months after commencing statin treatment (atorvastatin 20mg) in adults with T1DM over 40 years of age, with diabetes for more than 10 years, with established nephropathy, and with other cardiovascular risk factors.
Fibrates, nicotinic acid, bile acid sequestrants and omega-3 fatty acid compounds should not be offered for primary prevention.
Treatment with drugs blocking the renin-angiotensin system (RAS) should be commenced if BP is >135/85mmHg, or >130/80mmHg for those with albuminuria or more than two features of metabolic syndrome. A stepped approach, with the addition of selective beta-adrenergic blockers, low-dose thiazides and long-acting calcium-channel antagonists, rather than a combination of RAS anatagonists, is advised.
Digital retinopathy screening and assessment of visual acuity should be undertaken in all newly diagnosed patients with T1DM and depending on the findings, patients should have annual screening, earlier review or referral to ophthalmology. Emergency review by an ophthalmologist should occur for:
- Sudden loss of vision
- Rubeosis iridis
- Pre-retinal or vitreous haemorrhage
- Retinal detachment
Rapid review should be undertaken for new vessel formation.
Referral to ophthalmology should be undertaken for maculopathy or pre-proliferative retinopathy.
All adults with T1DM should undergo annual assessment of an early morning urine for the estimation of albumin:creatinine ratio. Commence ACE inhibitors and titrate to full dose in those with microalbuminuria and maintain a BP <130/80mmHg. It is important to suspect and investigate for other causes of renal disease in the absence of progressive retinopathy, if BP is particularly high, if there is a sudden onset of gross proteinuria and nephrotic syndrome, and if there is coexisting haematuria.
Research has shown that an abnormal 10g monofilament test or absent pedal pulse identifies patients with moderate or intermediate risk of foot ulceration, while not surprisingly, a history of foot ulceration or lower extremity amputation identifies patients at high risk of foot ulceration.12 However, a normal neurological exam or 10g monofilament test does not detect early neuropathy and therefore should not be used to falsely reassure patients with T1DM that they do not have neuropathy.
Painful diabetic neuropathy (PDN) should be managed with pregabalin, gabapentin, duloxetine or amitriptyline.
Switch if the first choice is ineffective, taking into account overlap with the old treatment.
Do not use the following outside a specialist setting:
- Cannabis sativa extract
- Capsaicin patch
All patients with PDN should undergo a regular (six- to eight-weekly) clinical review to assess pain control, impact on daily activities, adverse events and continued need for treatment.
Be aware of the multiple manifestations of autonomic neuropathy, in the form of nocturnal painless diarrhoea, postural hypotension, delayed bladder emptying and rare manifestation of gustatory sweating. Enquire annually about erectile dysfunction and offer a PD-5 inhibitor if appropriate. If there is no benefit, refer for psychological or surgical management.
Gastroparesis and acute neuropathy
The management of gastroparesis is difficult, with limited effective antiemetic treatments. A small particle sized diet (mashed or puréed food) is suggested and CSII should be actively considered. Domperidone (in accordance with MHRA guidance), erythromycin and metoclopramide have shown benefit.
Acute painful neuropathy of rapid blood glucose control can be a debilitating but self-limiting condition. There is no evidence that relaxing glucose control benefits this condition. The pain is very severe, so it requires regular review, with maximal dose titration and if necessary, combination therapy, to limit side-effects.
1. Ahmad N, Thomas GN, Gill P et al. Lower limb amputation in England: prevalence, regional variation and relationship with revascularisation, deprivation and risk factors. A retrospective review of hospital data. J R Soc Med 2014; 107(12): 483-9
2. Liew G, Michaelides M, Bunce C. A comparison of the causes of blindness certifications in England and Wales in working age adults (16-64 years), 1999-2000 with 2009-2010. BMJ Open 2014; 4(2): e004015
3. Alva ML, Gray A, Mihaylova B et al. The impact of diabetes-related complications on healthcare costs: new results from the UKPDS (UKPDS 84). Diabet Med 2015; 32(4): 459-66
4. Cooke D, Bond R, Lawton J et al. Structured type 1 diabetes education delivered within routine care: impact on glycemic control and diabetes-specific quality of life. Diabetes Care 2013; 36(2): 270-2
5. Elliott J, Jacques RM, 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(7): 847-53
6. Damiano ER, McKeon K, El-Khatib FH et al. A comparative effectiveness analysis of three continuous glucose monitors: the Navigator, G4 Platinum, and Enlite. J Diabetes Sci Technol 2014; 8(4): 699-708
7. Maahs DM, DeSalvo D, Pyle L et al. Effect of acetaminophen on CGM glucose in an outpatient setting. Diabetes Care 2015; 38(10): e158-9
8. Roze S, Smith-Palmer J, Valentine W et al. Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in type 1 diabetes: a systematic review. Diabet Med 2015 May 11. doi: 10.1111/dme.12792
9. Azmi S, Ferdousi M, Petropoulos IN et al. Corneal confocal microscopy shows an improvement in small-fiber neuropathy in subjects with type 1 diabetes on continuous subcutaneous insulin infusion compared with multiple daily injection. Diabetes Care 2015; 38(1): e3-4
10. Mehra S, Boulton A, Tavakoli M et al. Corneal confocal microscopy detects early nerve regeneration after pancreas transplantation in patients with type 1 diabetes. Diabetes Care 2007; 30(10): 2608-12
11. Tavakoli M, Mitu-Pretorian M, Petropoulos IN et al. Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes 2013; 62(1): 254-60
12. Crawford F, Cezard G, Chappell FM et al. A systematic review and individual patient data meta-analysis of prognostic factors for foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS). Health Technol Assess 2015; 19(57): 1-210