Dr Daniel Lasserson looks at the evidence and advises on starting diabetes patients on insulin
The management of type 2 diabetes poses
a big challenge for primary care. There
are nearly 2 million people with type 2
diabetes in the UK and the incidence is
increasing. The disease is progressive and carries a high risk of vascular events. Interventions are focussed on reducing vascular risk by controlling blood pressure, reducing total and LDL cholesterol and optimising glucose control.
What the research says
What we know is that improving glucose control will reduce complications. The UKPDS study showed that in the long term a reduction in HbA1c from 7.9 per cent to 7.0 per cent resulted in a 25 per cent reduction in microvascular events1, but this level of reduction does not significantly reduce mortality and macrovascular complications. A target HbA1c of 6.5 per cent is recommended by the Joint British Societies as well as organisations in the US.
Diet, lifestyle and oral hypoglycaemic agents (OHAs) are the initial strategies to reach glycaemic targets. However, OHAs will ultimately fail to control glucose in the majority of people with type 2 diabetes2. New classes of OHAs (such as glitazones) have appeared on the market, which may improve glucose control compared with standard therapy but do not perform well enough in the long term and at best delay rather than replace the need for insulin.
A substantial proportion of people with diabetes in the UK and throughout Europe have poor glucose control despite the evidence base for treatment goals for type 2 diabetes, and the evidence for insulin use in the long term to reach these goals. Clearly there are barriers to translating this knowledge into patient care. To improve the care of people with type 2 diabetes we should address the factors that influence both doctor and patient.
Turning theory into practice
When considering insulin therapy, understanding the patients' attitudes is an important first step. This is often referred to as concordance: where patient and doctor reach a joint decision on whether and which medication will be appropriate for the patient. Surprisingly, little high-quality research has been carried out that analyses patients' health beliefs in this area.
One multinational study (including the UK) of patients who were not yet taking
insulin identified two themes3. One was that patients did not believe that insulin was going to work. The other was that
patients blamed themselves for needing
insulin therapy (although those that adhered to a diet and exercise regime were
less likely to self-blame). Self-blame was associated with greater worry about starting
insulin. The authors of this study recommended an educational programme to highlight insulin efficacy as well as to explain how progressive pancreatic ß-cell failure
results in the need for insulin. Incorporating health beliefs into discussions around
insulin initiation may help to reduce
patient 'resistance' to insulin.
Solving insulin dilemmas
The major dilemmas that face GPs in initiating insulin are timing of insulin therapy, choosing the insulin regimen and how
to help and support the patient. These
problems are less in secondary care where there is great clinical experience and
supportive resources among doctors and specialist nurses. In primary care, although some practices have developed their own
locally enhanced service in insulin
initiation, a significant proportion of GPs may feel under-prepared to take on the role of insulin prescriber and may look to
evidence and guidelines as an educational resource.
Using published research on insulin
initiation has limitations in primary care. The majority of studies recruit patients from secondary care, so the evidence base does not match the patients an average GP will see. Trial protocols have multiple early
follow-up appointments for adjusting
insulin doses and reviewing safety issues such as hypoglycaemic episodes. In a busy general practice setting, this close monitoring may not be feasible using routine
appointments. Furthermore, NICE has
commented that there is insufficient evidence to guide the choice of insulin regimen or insulin formulation.
Timing of insulin therapy may be crucial to long-term outcome as modelling suggests that early glucose control reduces diabetic complications. A mathematical model
using data from large trials, such as the UKPDS, suggests that bringing HbA1c to
target (<7 per="" cent)="" six="" months="" from="" diagnosis="" compared="" with="" 24="" months,="" confers="" a="" long-term="" benefit="" in="" risk="" of="" microvascular="" disease4.="" there="" are,="" however,="" no="" national="" guidelines="" on="" how="" quickly="">7>
patients with type 2 diabetes should
be controlled when HbA1c is above
Certain OHAs should be continued when starting insulin. This reduces the overall
insulin dose and reduces weight gain.
Current NICE guidance recommends
continuing metformin if part of pre-insulin combination treatment, and sulphonylureas should be continued if metformin was not tolerated or contra-indicated before insulin initiation.
Initial dosing and regimens of insulin have been suggested by several review articles based on the authors' experiences as well as some evidence from randomised clinical trials. A consensus statement from the European Association for the Study of Diabetes suggests a regimen based on basal intermediate-acting insulin (for example, NPH insulin) at bedtime, or basal long-
acting insulin (such as glargine) given once a day either at bedtime or in the morning5. This only involves one injection per day and usually can be started at 10 units or 0.2 units per kg.
In a more complex guideline from the US, the pattern of hyperglycaemia can be used to tailor a starting insulin regimen6. Using an initial dose of 0.15 units per kg, fasting hyperglycaemia is treated with basal
insulin, whereas a 'biphasic' mix of short and longer acting insulin is used where there is greater post-prandial hyperglycaemia. The complexity of a basal-bolus regime that combines control of fasting and post-prandial glucose needs greater monitoring of blood glucose and education about matching insulin requirements with food intake, and is unlikely to be a popular first choice with patients.
Inhaled insulins have been suggested as a possible solution to the problems of injectables, but their role in type 2 diabetes is unclear. Although they can reduce HbA1c in combination with OHAs, their use results in increased hypoglycaemia rates and weight gain. There are also issues concerning the effects on respiratory function that can only be answered by long-term trials.
NICE has ruled in its final appraisal determination that inhaled insulin can be prescribed to needle-phobic patients after assessment by a diabetes specialist, relaxing the need for psychological assessment, with all initiation and monitoring of response to be done at specialist diabetes centres. But even though NICE has concluded this (barring any last-minute appeals), the scale of the type 2 diabetes epidemic and the cost of inhaled insulin may preclude it as an affordable option on a wide scale.
It is likely that national guidance will improve the initiation of insulin in primary care. Guidelines from review articles are helpful but do not address the issues of optimum patient education and support that are likely to impact on concordance. Simplified regimes with educational and monitoring standards may result in earlier insulin initiation. Current NICE guidance is under review but the expected date of publication of updated guidance is February 2008.
Daniel Lasserson is an academic GP registrar at the department of public health and primary care at the University of Oxford and a GP registrar in Oxford
Acknowledgments to Dr Carl Heneghan, deputy director of the department of evidence-based medicine at the University of Oxford, for advice on this article
Competing interests None declared
Mr X is a 73-year-old man with mild learning difficulties who lives alone in sheltered housing with once-daily carers. He was diagnosed with type 2 diabetes four years ago and was initially managed with diet but after adding both metformin and gliclazide at maximal doses his HbA1c was still elevated at 8.8 per cent. Mr X wanted to keep his independence and accepted that reducing diabetic complications was best achieved with insulin.
His gliclazide was stopped and he was started on insulin glargine – 10 units before breakfast. The district nurses also monitored his blood sugar pre-injection, enabling measurement of fasting sugar to help with insulin titration. His fasting glucose was initially high at 12.7mmol/l and every three days the glargine was increased by two units until the fasting glucose was below 7mmol/l – this took two weeks and an eventual dose of 20 units glargine daily. Three months later his HbA1c was 7.3 per cent.
1 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352 :837-53.
2 Turner RC et al. Glycaemic control with diet, sulphonylurea, metformin or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999;281:2005-12.
3 Peyrot M et al. Resistance to insulin therapy among patients and providers. Results of the cross-national Diabetes Attitudes, Wishes and Needs (DAWN) study. Diabetes Care 2005; 28:2673-9.
4 Bailey CJ et al on behalf of the Global Partnership For Effective Diabetes Management. Earlier intervention in type 2 diabetes: The case for achieving early and sustained glycaemic control. Int J Clin Pract 2005; 59:1309–16
5 Nathan DM et al. Management of hyperglycaemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006; 29:1963-72
6 Hirsch IB et al. Real-World Approach to Insulin Therapy in Primary Care Practice. Clinical Diabetes 2005; 23:78-86.