Maturity onset diabetes of youth

MODY refers to a group of monogenic forms of diabetes with autosomal dominant inheritance. The causative mutations are all in genes that control production of insulin and thus MODY is characterised by relative insulinopaenia but ketosis is an unusual feature of MODY. Diagnosis can be confirmed by molecular genetic analysis. Treatment is by OHA or by insulin therapy depending on the type.

Lifestyle modifications

Management depends to some extent on the type of MODY, as defined by molecular genetic testing. However, all patients should still undertake 'lifestyle' modifications. Specifically, the patient should be advised to maintain an optimal weight, increase the amount of regular physical exercise in their daily life, stop smoking if they do and modify their diet.

Dietary modifications should aim for an ideal BMI (25kg/m2), avoidance of refined sugars, reduction of saturated animal fats, the majority of calories coming from complex carbohydrates, five portions of fresh fruit and vegetables per day and a caloric intake aimed at maintaining steady weight (~2,000 cal per day for women and ~2,500 for men). Much of this advice is summarised on the 'eatwell plate'.

Exercise

Unrealistic targets should not be set. Any increase in routine physical activity will be beneficial.

For many people, half an hour walking each day on most days of the week will represent a significant increase in their physical activity and will have tangible benefits in terms of reduction in weight and increase in general well being.

Smoking cessation

The leading cause of premature mortality in diabetes is ischaemic heart disease. Smoking cessation is therefore of paramount importance.

The potential benefits of smoking cessation should be promoted very strongly and patients should be offered professional help with smoking cessation which may take the form of group support, one to one counselling, pharmacological management of withdrawal symptoms and the like.

Much of this support is now freely available on the NHS in the UK.

 Oral hypoglycaemics

Sulphonylureas

The sulphonylureas will normally be used as a first line oral hypoglycaemic therapy. The preferred drugs in this class are usually gliclazide or glipizide. The maximum dose of the former is 160 mg bd and the latter 10 mg bd, usual starting doses being 80 mg and 5 mg od respectively.

Patients with MODY due to HNF1alpha mutations are often very sensitive to sulphonylureas and as little as 20 mg of gliclazide once to twice daily can be adequate to achieve excellent glycaemic control.

If a sulphonylurea alone is inadequate to achieve the desired level of glycaemic control, the next step is insulin therapy.

Thiazoledinediones (glitazones)

Insulin resistance is an unusual feature in MODY and there is therefore very little role for insulin sensitising drugs, such as the glitazones, in treating MODY.

Metformin

Insulin resistance is an unusual feature in MODY and there is therefore very little role for metformin therapy in treating MODY.

Insulin therapy

Insulin is used when a sulphonylurea alone is insufficient to attain adequate glycaemic control. At this point, the sulphonylurea is stopped and insulin is started either as a basal bolus regimen or as a twice daily biphasic insulin, much the same as for T1DM.

Patient education

Who should be taught self-monitoring of glucose levels? 

Well controlled, stable glycaemia on sulphonylurea therapy in MODY is probably adequately monitored by periodic HbA1c testing. However, if the patient takes insulin, if there is any suspicion of recurrent hypoglycaemia regardless of treatment modality or if the patient wishes to, these are all indications for performing self-monitoring of glucose levels.

What topics should be covered in general diabetes education at presentation? 

This is a large and important subject and it is important that the diabetes specialist nurses spend considerable time with newly diagnosed MODY cases covering several important topics.

These include hypoglycaemia recognition and self management, sick day rules, and if they are insulin treated: Injection sites, driving, diet, adjusting insulin doses, use of insulin injection devices (including storage of insulin), changing cartridges and needles, recognising potential injection device failure. For female patients, contraception and pre-pregnancy planning should also be covered.

How are patients taught to adjust their insulin doses? 

Titrating insulin doses is an important part of self-management for patients with insulin treated diabetes.

While a minority of patients take fixed doses of insulin regardless of dietary intake and variations of physical activity this approach rarely produced good glycaemic control and, especially for patients on basal bolus regimens, it means that the patient is not realising much of the potential benefit of the flexibility of such a regimen.

It is usual for the dose of basal insulin to be kept fairly constant and most of the adjustments to be made on the prandial insulin. Some experienced patients learn empirically how much rapid acting insulin they need with meals of varying size and composition. Other patients develop a habit of testing their blood sugar and reacting to the result by adjusting the size of the next dose of rapid acting insulin, sometimes giving extra doses in between meals.

However, many would discourage this approach as it tends to promote a relatively unstable blood sugar oscillating between low and high blood sugars.

Formal systems for dose adjustment include carbohydrate counting. Another approach used by some patients is to record blood sugars and dietary intake and to regularly consult with their DSN who will advise on future adjustments to insulin doses based on the results. This system has the advantage of being both educational and therapeutic but is quite labour-intensive.

What are sick day rules?

Sick day rules are guidelines for patients on insulin giving advice on how to manage blood sugars and insulin doses during times of illness, especially illnesses that lead to reduced food intake and/or vomiting.

During these times, the cardinal advice is that patients should not stop their insulin. Insulin requirements often actually rise during intercurrent illness, even if food intake has significantly fallen.

Thus patients are advised to regularly check BMs (two to four hourly), continue their regular doses of insulin and counter any falling blood sugars with frequent small sips of a sugary drink.

If BMs are rising, they should take additional rapid acting insulin and test urine for ketones. If ketonuria >2+, worsening vomiting or progressive deterioration in their condition occurs, they should seek medical attention and/or admission to hospital.

Read more on sick day rules. 

What are the recommended precautions around driving? 

The mainstay of safe driving in people with diabetes is the avoidance, recognition and appropriate management of hypoglycaemia.

Thus, patients are advised to check their BM before getting in the car and to not set off if it is low until this has been rectified, to stop and check BM periodically during long journeys and to keep a source of rapidly absorbable carbohydrate, such as dextrose tablets, in the car.

If the patient does feel hypoglycaemia coming on they should pull over at the side of the road as soon as it is safe to do so, check their BM, ingest rapidly absorbed carbohydrate followed by a source of longer-acting carbohydrate and not proceed until their BM is back to a safe level and they feel well enough to continue.

The DVLA regularly re-assess the driving-safety of insulin-treated patients with diabetes by questionnaire to the patient and their doctor. The medical questionnaire includes an assessment of the patients knowledge of the above guidance.

Patients with significant hypoglycaemia unawareness may have their licence suspended by the DVLA for a period until some awareness has been restored.

Read more on driving.

What should pre-pregnancy counselling cover? 

The most important message for pre-pregnancy counselling in diabetes is that unplanned pregnancies should be avoided as far as possible.

While the foetal and maternal risks of pregnancy in diabetes are elevated in comparison with the background population risks, these can be significantly reduced by scrupulous glycaemic control, especially around the time of conception, and thus unplanned conception should be avoided.

It is therefore essential that young women with diabetes have these considerations explained to them and that they are encouraged to use effective contraception until such time as they are ready to conceive.

Prior to attempting to conceive they need to lower the HbA1c to around 7% (53 mmol/mol) and aim to achieve fasting blood sugars in the region of 6 mmol/L or less and post prandial blood sugars around 8 mmol/L or less. These are targets that should be maintained throughout pregnancy but are now thought to be most important of al around the time of conception.

Other factors to consider are the cessation of smoking, avoidance of alcohol and use of folic acid at neural-tube defect prevention doses (i.e. 5 mg/day).

Read more about pregnancy. 

What does good dietetic advice include? 

Dietary advice for people with diabetes should be little different from general healthy eating advice.

Specifically, avoidance of refined sugars, reduction of saturated animal fats, the majority of calories coming from complex carbohydrates, five portions of fresh fruit and vegetables per day and a caloric intake aimed at maintaining steady weight (~2,000 cal per day for women and ~2,500 for men).

Much of this advice is summarised on the 'eatwell plate'. One particular aspect of relevance to patients treated with insulin is the carbohydrate content of meals as this is a major determinant of prandial insulin requirements. This can be assessed by a system known as carbohydrate counting.

What is carbohydrate counting? 

Carbohydrate counting is a system for estimating the carbohydrate content of a meal by eye. It requires skill and takes time to learn. However, with practice it becomes a very useful to self-management tool.

The system involves patients learning to recognise standard quantities and types of food-stuff which can be done in practical sessions with dieticians or from books containing photos of plates of food.

Examples include 1 medium size boiled potato = 10 g carbohydrate. One slice white bread (standard thickness) = 15 g carbohydrate. With experience, the patient also learns how much prandial insulin they require per 10 g carbohydrate and thus after inspecting a plate of food can then accurately estimate the required dose of prandial insulin to take with that meal.

Carbohydrate counting is an important component of the DAFNE system.

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