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What you need to know about Type 1 diabetes

Endocrinologist Dr Colin Johnston answers GP Dr David Morris’s questions

Endocrinologist Dr Colin Johnston answers GP Dr David Morris's questions

1. Do you have any tips on how GPs can quickly spot a patient with late-onset type 1 diabetes, minimising the risk of ketoacidosis?

41227483Correctly diagnosing diabetes is becoming more difficult. Latent autoimmune diabetes in adults (LADA) is much more common than we used to think and has been said to account for up to 10% of all patients diagnosed as having type 2 diabetes.

As yet however there is no evidence that early diagnosis and use of insulin is beneficial. LADA is a slowly developing condition so – unlike young patients with type 1 diabetes – the risk of rapid metabolic decompensation and development of ketoacidosis is low.

LADA can be detected by measuring antibodies, islet-cell (ICA) and glutamic-acid decarboxylase (GAD) and I would recommend measurement at or soon after the diagnosis in younger patients (under 40), especially if lean. The clinical benefit of these measurements in older patients is still a subject for research and the timing of insulin therapy will be determined clinically.

An algorithm that may be helpful can be found on the online version of this article at pulsetoday.co.uk/clinical.

2. Is there any place for using oral hypoglycaemic agents, such as metformin and pioglitazone, in some patients with type 1 diabetes to reduce insulin dosage?

Yes. As more patients with type 1 diabetes are becoming obese and insulin resistant, the use of insulin sensitisers such as metformin is increasing.

There is evidence that metformin can improve or maintain glycaemic control with less weight gain than just increasing the dose of insulin. There is little data on the use of pioglitazone in type 1 diabetes and concerns over side-effects and licensing are likely to limit its use.

3. Last year, a BMJ paper concluded that aspirin had no benefit in the primary prevention of cardiovascular events in patients with diabetes. Should we now restrict aspirin to just those diabetes patients with established cardiovascular disease?

Neither the trial to which you refer, POPADAD (the Prevention Of Progression of Arterial Disease And Diabetes trial), or another recent Japanese trial found aspirin to be beneficial but both were underpowered to really answer the question. We will probably have to wait for the results of another, the ASCEND trial, which is some years off.

I think we can conclude that the benefits of aspirin in primary prevention are likely to be small, and routine use unjustified. But in those at higher risk, especially with hypertension and without contra-indication, it is probably still justified.

4. When would you recommend patients with type 1 diabetes begin taking a statin for cardiovascular protection? Are there any diabetes patients who ultimately you would not offer a statin to?

Unfortunately there are no trials on the use of statins in type 1 diabetes but we do know that the risk of macrovascular disease is increasing and is now the major cause of mortality in younger patients with the condition, so use of statins in those at high risk seems sensible.

Statins are contraindicated in pregnancy so I would be wary of recommending them to women of child-bearing age, but use in males who have had diabetes for longer than 20 years, especially with other risk factors such as microalbuminuria and hypertension, is probably justified. Otherwise, as indicated by NICE, use should be the same as recommended for those without diabetes.

5. Newer monitoring devices for diabetes incorporate testing for blood ketones. Can you advise how GPs could use and respond to blood ketone measurements?

Routine availability and measurement of blood ketones in patients with type 1 diabetes is still controversial. There is some evidence that in particular settings and with careful patient education use can improve management of hyperglycaemia and reduce the incidence and severity of ketoacidosis, but the key is careful patient education and I don't think we have the evidence to support widespread use.

I would recommend discussion of individual patients with the specialist diabetes team.

6. I am, whenever possible, treating patients with type 1 diabetes who have microalbuminuria or proteinuria with an ACE-inhibitor or ARB. What does the evidence suggest about using these two agents in combination for renoprotection and what problems might arise if I do?

There is considerable evidence that blockade of the renin-angiotensin system

in diabetes reduces proteinuria, improves blood pressure and delays the progression of renal impairment. In type 1 diabetes the majority of the trials used ACE inhibitors while in type 2 similar results have been seen with ARBs.

In patients already on maximal doses of ACE inhibitor the combination with an ARB can further reduce proteinuria with the assumption, as yet unproven, that this will provide further renal protection. The combination is usually well tolerated, so long as those with significant renovascular disease are excluded.

7. What issues do we need to address in women with type 1 diabetes who plan to become pregnant? I am particularly interested in your advice regarding optimising antihypertensive regimes.

The evidence is now overwhelming that good glycaemic control and the avoidance of teratogenic drugs at the time of conception improves outcome. This can be achieved by early identification and referral to specialist pre-pregnancy clinics.

Statins should be discontinued, which – for a few months – should not be harmful.

ACE inhibitors need to be avoided and for hypertension other agents proven to be safe in pregnancy should be used, such as methyldopa. For some, with nephropathy, this can result in a significant increase in proteinuria which is likely to get worse during pregnancy and may not revert post delivery. Careful counselling is required.

These patients are also at high risk of progressive retinopathy so retinal screening before and during pregnancy is required.

8. I understand the UK has among the lowest use of insulin pumps in Europe. Why is this, and should we be getting more patients on to them? Which patients are most likely to benefit from a pump?

There are clear differences in the use of pumps between countries and between centres within the UK. The reasons are less clear and probably – at least in part – reflect the enthusiasm of the specialist team.

In adults, when compared with multiple injections with analogue insulins, pump therapy is associated with only very modest improvements in glycaemic control, although it can achieve this with lower rates of hypoglycaemia. Some studies indicate an improved quality of life but most of the patients are pre-selected.

What is important, as per NICE guidance, is that all patients with either sub-optimal control (HbA1c of 8.5% or more) or frequent hypoglycaemia should have a proper discussion about the use of a pump.

But widespread use in the UK probably won't happen until we have systems where glucose sensors can link to pumps, adjusting doses directly, avoiding the need for frequent capillary glucose monitoring. Such systems are under development and trial at the moment.

9. I've had a few patients with type 1 diabetes inquiring about the DAFNE dietary programme. This isn't yet available in our area although I understand it is due to be rolled out across the country. Can you explain the basis of the programme and the benefits it could offer?

DAFNE stands for dosage adjustment for normal eating and is an educational programme to help patients with type 1 diabetes on insulin understand the factors that influence insulin demand and adjust their own doses, especially in relation to different foods and exercise.

There is evidence that it can help improve glycaemic control (modestly) and quality of life with diabetes. DAFNE is delivered in a group format on consecutive days. There are others used in the UK (such as BERTIE) delivered on a daily basis, over some weeks, with evidence for similar benefit but no comparative data.

NICE recommends all patients should have the opportunity to participate in an educational programme and the important thing is to try to ensure that patients have the opportunity to attend one.

10. Last week a patient asked me about the possibility of islet cell transplantation. Could you bring me up to date on the subject and outline the pros and cons of such a procedure?

Islet cell transplantation is still very experimental. We have proof of concept and the technique works, but there are problems of islet availability, the need for ongoing immunosuppression, side-effects, and the fact that function is finite and most patients will require ongoing intervention every few years.

Within the UK we have a national programme with six identified centres, which should help to find solutions to the above problems but it is unlikely to be a realistic ‘cure' for many patients where the proven safety and success of long-term insulin therapy make the risk unjustified. Stem cell technology may hold the key but is at least some years off.

But islet cell transplant may still be a realistic option for patients with severe complications, especially severe hypoglycaemia with unawareness and normal renal function. For those with renal failure a better option is a combined renal/pancreatic transplant.

Dr Colin Johnston is consultant physician and endocrinologist at West Herts Acute Trust

Competing interests Dr Johnston has received sponsorship from Novo Nordisk and Aventis to attend educational meetings

Type1 diabetes What I will do now What I will do now

Dr Morris considers the responses to his questions

The author's comments on latent autoimmune diabetes in adults make interesting reading.
I'll have a lower threshold for considering LADA in the lean ‘type 2' diabetic patient, especially if younger, and plan to make use of antibody tests to assist diagnosis. And it's reassuring to read that rapid deterioration to ketoacidosis is unlikely.
I'm also encouraged to expand my use of metformin in overweight patients with type 1diabetes who may be strongly insulin resistant.
In addition to reducing insulin requirements, metformin may provide cardiovascular benefit and limit further weight gain. I'm still uncertain about offering aspirin for primary prevention but I think I'll be most likely to use it in those patients who have additional cardiovascular risk factors.
In those diabetes patients with microalbuminuria or proteinuria I'll be more likely to consider using the combination of
ACE-inhibitors and ARBs, while keeping in mind the need to monitor carefully for hyperkalaemia and deteriorating renal function.
Although I agree that routine blood ketone monitoring by patients isn't helpful, our specialist diabetes team will continue using this to help assess acute uncontrolled hyperglycaemia when there is a risk of progression to ketoacidosis.

Dr David Morris is a GP in Shrewsbury, Shropshire

thps t1d

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