Diabetes - The Global Challenge


Dr Maria Barnard, Lead Consultant in Diabetes
The Whittington Hospital NHS Trust London
Honorary Senior Lecturer, University College London Medical School


Diabetes mellitus is a major global health challenge. In 2007, around 246 million people worldwide were living with diabetes and that number is predicted to increase to 380 million by 2025. In the UK, the number of people with diabetes could reach three million by 2010. Already each day in the UK, £10 million is spent on treating diabetes and diabetic complications, including heart disease, stroke, blindness, kidney disease and amputations. People with diabetes may also develop severely abnormal blood glucose (sugar) levels, requiring urgent medical attention. All this means that people with diabetes have a reduced life expectancy. Worldwide, every ten seconds, a person dies from diabetes-related causes.


How is Diabetes Diagnosed?


Diabetes is diagnosed by detecting an increased glucose level on a blood sample. If this does not give a definite answer, an oral glucose tolerance test (OGTT) is done, when blood glucose is measured before and 2 hours after having a glucose drink.

In some people, the blood glucose level is not high enough to diagnose diabetes, but is not low enough to be classified normal. This “impaired glucose tolerance” or “pre-diabetic syndrome” can be a precursor to developing diabetes.

Diabetes diagnosed:

Random blood glucose

³ 11.1 mmol/l

Fasting blood glucose

³ 7.0 mmol/l

OGTT: 2 hour glucose

³ 11.1 mmol/l


What Causes Diabetes?


Insulin lowers blood glucose levels. It is released from islet ß-cells in the pancreas into the bloodstream. It controls the transfer of glucose out of the blood and into cells, where it is used to create energy. Diabetes occurs when there is not enough insulin in the body (insulin deficiency) or when the body becomes resistant to the effects of insulin (insulin resistance).

Some famous people with diabetes:

Christopher Biggins

Sir Steve Redgrave

 Halle Berry

Different Types of Diabetes 


Type 1 diabetes:

Affects 5-10% of people with diabetes and is most commonly diagnosed in childhood. It is caused by autoimmune destruction of the ß-cells, when antibodies are made that directly attack these insulin-producing cells. People are born with a genetic tendency to develop type 1 diabetes, which is then triggered possibly by exposure to a viral infection.


Type 2 diabetes

This affects 90–95% of people with diabetes and is usually diagnosed in people aged over 40 years. It is caused mainly by resistance to the effects of insulin. Obesity is a major risk factor for type 2 diabetes, which is therefore greatly on the increase. Other risk factors include having a family member with type 2 diabetes. People from some ethnic groups are at risk of developing type 2 diabetes: in the UK, there is a significant risk of diabetes occurring in people of Indo-Asian, Black-Caribbean or Black-African descent.


There is a large collection of other conditions that can lead to diabetes, including thalassaemia.

Diabetes in thalassaemia is thought to be caused mainly by iron overload, from repeated blood transfusions, damaging the pancreas. However, there may be other factors. Insulin secretion may be reduced, possibly because iron is directly toxic to the insulin producing pancreatic ß-cells. 

But there is also evidence in some people with thalassaemia for an autoimmune reaction against ß-cells. Insulin resistance may occur in thalassaemia, caused by liver disease from iron overload or hepatitis C virus infection. Some patients with thalassaemia and diabetes have both insulin deficiency and insulin resistance. 

Furthermore, with the worldwide diabetes epidemic, a person with thalassaemia and raised blood glucose could have developed type 1 or 2 diabetes. The situation can be very complex. However, understanding the underlying cause of diabetes in an individual is essential for logical treatment decisions.


What Symptoms does Diabetes Cause?


Excess glucose in the blood is cleared by being excreted in the urine, carrying water with it. Diabetes can cause symptoms of being thirsty, passing a lot of urine, weight loss and tiredness. When there is a severe insulin deficiency, as in type 1 diabetes, these symptoms can occur rapidly over 2-4 weeks and if untreated, can lead to profound dehydration and kidney failure. With insulin resistance, as in type 2 diabetes, there is a more gradual increase in blood glucose levels. These symptoms tend to develop much more slowly and people may have type 2 diabetes for years before being diagnosed.


For people with thalassaemia who develop diabetes, their symptoms will depend on how insulin deficient and how insulin resistant they are. However, with modern iron chelation therapy, generally people with thalassaemia gradually develop diabetes and many have no initial symptoms. Some thalassaemia services will therefore screen their patients once a year, measuring the fasting blood glucose level or performing an OGTT.


Why is it Important to treat Diabetes?

Advanced CataractThe main aim in treating diabetes is to prevent diabetic complications. Diabetes damages blood vessels and various organs. In the eyes, diabetes can cause early cataracts (a cloudy lens in the eye). It can also damage the blood vessels supplying the back of the eye with oxygen and nutrients.

This is called diabetic retinopathy and it is the commonest cause of blindness in working-age adults in the UK.

Retinal photograph (early retinopathy)In the kidneys, diabetes can damage the small blood vessels which carry

 blood through for the kidneys to clean. This is called diabetic nephropathy and in the early stages it causes no symptoms. It is detected by measuring increased protein levels leaking through into the urine (microalbuminuria, then proteinuria). As the damage progresses, the kidney function deteriorates and dialysis or kidney transplant may be needed.


Diabetes can damage the small blood vessels supplying nerves, causing loss of function. This is called diabetic neuropathy and it particularly damages sensation in the feet, causing numbness and possible severe damage, such as foot ulcers.

Diabetes can damage the larger blood vessels in the heart and brain. Lumps of fatty material containing cholesterol narrow these blood vessels (atherosclerosis). Eventually blood flow can be completely blocked by a small overlying blood clot. This can damage the heart muscle (heart attack) or brain (stroke).

Preventing these complications is a critical aim of diabetes management. This can be done by both tight blood glucose control and by controlling all other factors that can damage blood vessels.

Measure

Target

Measure

Target

Fructosamine

[*HbA1c

< 299 umol/l

< 6.5 %]

Blood pressure

- with nephropathy

< 130 / 80

< 125 / 75

Blood glucose before meals

Blood glucose after meals

4 – 7 mmol/l

5 – 8 mmol/l

Aspirin if > 40 years of age or cardiovascular risk

75 mg daily

Smoking status

Non-smoker

Total cholesterol

< 4.0 mmol/l

Exercise

Daily

LDL cholesterol

< 2.0 mmol/l

Body mass index

20 – 25 kg/m2

Triglycerides

< 1.7 mmol/l

*HbA1c is the most widely used measure of average blood glucose control in diabetes.

 It is not used in thalassaemia because repeated blood transfusions make it inaccurate.

 

There has been a belief that people with thalassaemia and diabetes have a much lower risk of developing diabetic complications. However, I think that will be challenged in the future. 

The successful management of thalassaemia is now leading to a significantly increased lifespan.

If diabetes is also present, there will be a much greater opportunity for diabetic complications to develop, which we are beginning to see in our patient population.

 

How should diabetes in thalassaemia be managed?


Ideally, with the best iron chelation therapy, iron overload diabetes will not occur in thalassaemia. This is the great future hope. However, worldwide diabetes is increasing so much that type 1 or 2 diabetes may occur in a person with thalassaemia. In thalassaemia, screening allows raised blood glucose levels to be detected at an early stage. At this stage of abnormal glucose tolerance, intensive iron chelation may prevent diabetes developing or can even revert blood glucose levels to normal. In addition, weight loss and exercise are both established ways to reduce insulin resistance and to prevent progression to diabetes.

 

Once diabetes develops, some oral antidiabetic drugs have been tested in thalassaemia. There are reports on the successful use of sulphonylureas and acarbose. Sulphonylureas (e.g. glibenclamide, gliclazide, glimepiride) lower blood glucose by increasing insulin release from pancreatic ß-cells. Acarbose inhibits the digestion of starch and sugars in the gut, reducing the rise in blood glucose after food. For type 2 diabetes, metformin is the first choice treatment but there is little research on its use in thalassaemia. Metformin reduces insulin resistance and can protect against cardiovascular disease. It could be equally promising in thalassaemia and we certainly consider using metformin.

 

For the many patients with thalassaemia who are insulin deficient, insulin is an essential daily treatment. Insulin must be injected (into the fat immediately below the skin). There are two main treatment regimens. The first uses biphasic insulins (e.g. NovoMix 30, Humalog Mix50) injected twice daily. These contain a mixture of rapidly acting and slower acting (intermediate) insulins, given 

before breakfast and before the evening meal.


The basal/bolus insulin regimen is the other main option. A very slow-acting (basal) insulin is given once a day (e.g. Glargine {Lantus}, Detemir {Levemir}) to give background 24 hour insulin cover. Then, every time a person eats carbohydrate they inject a rapid acting (bolus) insulin (e.g. NovoRapid, Humalog), which controls the blood glucose rise from the food. This requires multiple daily injections of insulin. Also, to get good blood glucose levels, patients need to learn how to adjust their insulin dose according to the carbohydrate content of the food.

For people with type 1 or 2 diabetes, there are education courses based on small groups of people working together, discussing all aspects of living with diabetes with trained tutors. These courses can improve diabetes control and quality of life. There has been no research into developing courses for people living with thalassaemia and diabetes. However, people with thalassaemia and insulin dependent diabetes have attended our type 1 diabetes course (WINDFAL) and found this a useful and valuable experience.

One of the most effective settings for clinicians to look after a person with thalassaemia and diabetes is in a joint clinic. Here members of both diabetes and thalassaemia teams work together with patients. This enables staff to manage all the complex needs of these two conditions and it allows staff to learn from each other and provide a consistent approach.

Conclusion


Managing diabetes is one of the greatest challenges that a person with thalassaemia can face. Training people to self-manage their diabetes and providing support from specialist teams working together are critical for excellent diabetes control. Only then will we see people with thalassaemia and diabetes achieving a long and healthy life.

References and useful websites:


 Diabetes UK: information, policy statements and campaigning