Diabetes

There are two main types of diabetes: Type 1 (which used to be called insulin dependent diabetes or juvenile onset diabetes) and Type 2 (which used to be known as non-insulin dependent diabetes or adult onset diabetes). In addition, Gestational Diabetes is a term used to describe diabetes which is recognised for the first time during pregnancy. Pancreatic disease or damage can also cause diabetes if the insulin producing beta cells are destroyed and there are also rare genetic causes.

Type 1 diabetes develops if the body can no longer produce insulin. It accounts for approximately 10% of diabetes cases in the United Kingdom and is usually diagnosed in those under the age of 30. Symptoms commonly develop abruptly and the diagnosis is often made following an emergency admission to hospital. The patient may be seriously ill, even unconscious, with very high glucose levels and high levels of ketones.

Patients with Type 1 diabetes make very little or no insulin. Any insulin producing beta cells that patients have at the time of diagnosis are usually completely destroyed within 5 to 10 years leaving them entirely reliant on insulin injections. The exact cause of type 1 diabetes is unknown, but a family history of diabetes, viruses that injure the pancreas, and autoimmune processes (where the body's own immune system destroys the beta cells) are all thought to play a role. As type 1 diabetes has an earlier age of onset and hence longer duration, patients may have more severe medical complications than other forms of diabetes.

Those with Type 2 diabetes do make their own insulin but it is either not in a sufficient amount to meet their needs and/or their body has become resistant to its effects. At the time of diagnosis they may have typical symptoms of diabetes, especially thirst, weight loss or may be passing large amounts of urine or they may not have any symptoms. Many people may be undiagnosed, as fairly asymptomatic, for years meaning that long-term complications of the disease can be present at diagnosis. The diagnosis may can be made on finding high glucose concentrations in the blood. About 90% of diabetes cases in the United Kingdom are type 2. It generally occurs later in life, in those who are obese, sedentary and over 45 years of age. Risk factors include:

• Weight excess / obesity
• Lack of exercise
• A family history of diabetes
• Any abnormality of glucose tolerance – the oral glucose tolerance test (OGTT) may identify individuals whose ability to handle a high glucose meal is not normal but is not sufficiently abnormal to diagnose diabetes
• Ethnic groups - more common in Asian and African-Caribbean communities
• History of gestational diabetes or baby weighing more than 4.5 kg
• Metabolic syndrome, showing several abnormalities e.g. high triglycerides, high cholesterol, low HDL, high blood pressure, gout or fatty liver

Because the population of the western world is becoming more obese and not getting enough regular exercise, the number of those developing type 2 diabetes is rising and, of particular concern is its development in young people.

Gestational diabetes is a temporary type of hyperglycaemia (high blood glucose concentration) seen in some pregnant women, usually during the second or third trimester. The cause is unknown, but it is thought that some hormones from the placenta increase insulin resistance in the mother causing elevated blood glucose concentrations. In the UK, gestational diabetes is usually diagnosed by an oral glucose tolerance test carried out, either because high glucose concentrations have been found in the urine or blood or because the women is known to be at risk for the condition (obesity, a family history of Type 2 diabetes, , a previous baby weighing 4.5 kg or above, previous gestational diabetes, minority ethnic family origin with a high prevalence of diabetes).

Testing is usually performed between the 24th and 28th week of pregnancy. If gestational diabetes is not treated, the baby is likely to be larger than normal, be born with low glucose levels, and be born prematurely. Gestational diabetes also raises the risk of eventually developing type 2 diabetes, for both the mother and the baby.

Prediabetes, often referred to as impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), is characterised by glucose levels that are higher than normal but not high enough to be diagnostic of diabetes. Usually those who have prediabetes do not have any symptoms but if nothing is done to lower their glucose concentration and HbA1c, they are at an increased risk of developing diabetes within about 10 years. HbA1c is a long-term marker of glucose control, glucose can become ‘stuck’ to haemoglobin within red blood cells and the rate this occurs is proportional to the average glucose concentration. This therefore gives a good indication of average sugar levels over the preceding 3 months.

In the UK all non-pregnant individuals aged 40 or above, or 25 and above from high risk black and ethnic minority groups; and those with a condition that increases the risk of diabetes, are eligible to be screened for diabetes. For those being risk assessed, a combination of assessment tools, fasting glucose concentration and HbA1c can be used.

Other causes of diabetes

There are a variety of less common causes of diabetes. Any condition that damages the pancreas and/or affects insulin production or usage can lead to the development of diabetes.

Latent autoimmune diabetes in adults (LADA) is a slowly progressing type 1 diabetes that is often misdiagnosed as type 2 diabetes. Those who have it tend to produce some of their own insulin when first diagnosed and most have diabetes autoantibodies.

Monogenic diabetes is a group of causes associated with faulty genes that affect the body's ability to produce insulin:

• MODY – Maturity onset diabetes of the young is a type of diabetes that is caused by a gene mutation. Several different genes that affect the production of insulin are grouped under MODY. This is an inherited cause of diabetes that is typically detected in children or adolescents, but some people develop it later and some do not develop diabetes.
• NDM – Neonatal diabetes mellitus is a rare type found in newborns and young infants. Diagnosis is complicated by the presence of hyperglycaemia in any newborn in the first couple of days, which is even more common if premature or non-specifically unwell. High blood glucose without an obvious cause, found from a blood test e.g. from a heel prick, can indicate the diagnosis. The baby may have no symptoms or have polyuria, evidence of dehydration or be irritable.

Conditions that block or damage the pancreas can lead to the development of diabetes. Examples include:

• Cystic fibrosis produces thick mucus that can block the release of pancreatic enzymes and damage the pancreas.
• Haemochromatosis is an inherited condition associated with increased iron storage. Iron accumulation can damage the pancreas and other organs. It is sometimes referred to as "bronze diabetes" because the excess iron can turn a person's skin a bronze colour.
• Pancreatitis, pancreatic cancer, and other pancreatic diseases that damage the pancreas and/or beta cell production
• Pancreas trauma or removal

The signs and symptoms of diabetes are related to high blood glucose levels (hyperglycaemia), temporarily low glucose levels (hypoglycaemia), and to complications associated with diabetes. The complications can be related to lipid (fat) production, to macrovascular (large blood vessel) or microvascular (small blood vessel) damage, for example kidney (diabetic nephropathy), nerve (diabetic neuropathy), and eye (diabetic retinopathy) damage, and/or to the slower healing associated with diabetes. Diagnosis is complicated by the presence of hyperglycaemia in any newborn in the first couple of days, which is even more common if premature or non-specifically unwell. High blood glucose without an obvious cause, found from a blood test e.g. from a heel prick, can indicate the diagnosis. The baby may have no symptoms or have polyuria, evidence of dehydration or be irritable. Patients with Type 1 diabetes are often diagnosed with acute severe symptoms that require hospitalisation. With early type 2 diabetes, prediabetes and gestational diabetes there may be no symptoms.

Symptoms of hyperglycaemia may include any of:

• Increased thirst
• Passing increasing amounts of urine
• Increased appetite (with type 1 weight loss is also seen)
• Tiredness
• Feeling sick
• Vomiting
• Stomach pain (especially in children)
• Blurred vision
• Slow-healing infections
• Numbness, tingling, and pain in the feet
• Erectile dysfunction in men
• Absence of menstruation in women
• Rapid breathing (acute)
• Decreased consciousness, coma (acute)

Symptoms of impending hypoglycaemia:

Temporary hypoglycaemia in the diabetic patient may be caused by the accidental injection of too much insulin, not eating enough or waiting too long to eat or exercising strenuously. Hypoglycaemia needs to be treated because, if it is severe, it can rapidly progress to unconsciousness. True hypoglycaemia occurs when the blood sugar is below 2.5 mmol/L, though symptoms may develop earlier, especially if the blood sugar falls rapidly, and include:

• Sensation of hunger
• Headache
• Anxiety
• Sweating
• Confusion
• Trembling
• Weakness
• Double vision
• Convulsions (severe)
• Coma (severe)

In general there are multiple symptoms or complications; notable examples include:

• Wound infections, especially on the feet. They are slow to heal and if not adequately treated could eventually lead to amputation. Aggressive and specialised measures are often necessary
• Vision problems, diabetic retinopathy can lead to eye damage, a detached retina, and to blindness. Laser surgery may be necessary
• Urinary tract infections which may be frequent and resistant to antibiotic treatment

There may also be additional symptoms linked to specific underlying conditions, such as haemochromatosis and cystic fibrosis.

Diabetes is diagnosed by measurement of glucose in blood (or more correctly in plasma which is the fluid left behind when cells have been separated from blood) in accordance with the criteria of the World Health Organisation.

Either random or fasting measurements or the measurements made during an oral glucose tolerance test (OGTT) may be used. The OGTT involves a fasting glucose, followed by the patient drinking a standard amount of a glucose solution to "challenge" their system, followed by another glucose blood test two hours later. In an individual with typical symptoms, diabetes is diagnosed by finding either a random plasma glucose concentration greater than 11.0 mmol/L or a fasting plasma glucose concentration greater than 7.0 mmol/L or a plasma glucose concentration greater than 11.0 mmol/L two hours after taking 75g of anhydrous glucose in an OGTT. HbA1c (also called haemoglobin A1c or glycohaemoglobin) evaluates the average amount of glucose in the blood over the last 2 to 3 months and has mostly replaced the other tests to screen for diabetes, diagnosed if HbA1c is 48 mmol/mol or above.

In the absence of typical symptoms, diagnosis should not be based on a single glucose measurement but requires confirmation by at least one further glucose test result on another day with a value in the diabetic range.

Sometimes random urines are tested for glucose, protein, and ketones during a routine clinical examination using a 'dipstick test'. Diabetes may be indicated if glucose and/or ketones are present but this test is not sensitive or specific enough for diagnosing or monitoring patients.

Patients with diabetes can monitor their condition by measuring their own blood glucose level. Home blood measurements are done by placing a drop of blood, obtained by pricking the finger with a small lancet device, onto a plastic glucose test strip and then inserting the strip into a small test meter, which provides a digital readout of the blood glucose concentration. Glucose measurements can be made several times a day at a frequency which depends on how well blood glucose concentration is controlled and what treatments are being taken. Frequency will be guided by advice from the diabetes team and what is appropriate for the individual for example driving for prolonged periods or heavy exercise may require additional testing.

Several laboratory tests may be used to monitor diabetes on a regular basis.

To monitor glucose control:
Glucose, Haemoglobin A1c (HbA1c) Glucose is commonly available via finger prick methods. Desk top analysers are available for HbA1c which allows some clinics to measure this at the appointment e.g. paediatric clinics. The slight complication for HbA1c is that people with haemoglobin variants e.g. thalassaemia, may give abnormal results that are related to the haemoglobin, not the glucose concentration. Therefore this measurement remains suited for laboratory assay, at least until the individual is known not to have a variant haemoglobin.

To monitor kidney function:
Creatinine, Creatinine Clearance, Microalbuminuria (A test which detects very small quantities of albumin in the urine and can indicate early kidney damage. It is measured as the Albumin Creatinine ratio (ACR) or Albumin Excretion rate)

To monitor lipids (fats):
Triglycerides, cholesterol, HDL cholesterol, LDL cholesterol.

In addition to diabetes tests listed above, a few other tests may be used in the evaluation of the type of diabetes:

• Diabetes autoantibodies – this test may help distinguish between type 1 and type 2 diabetes if the diagnosis is unclear. The presence of one or more of these antibodies indicates type 1 diabetes.
• Insulin, C-peptide – indicate if pancreas is still producing insulin
• Urine and/or blood ketone tests may be ordered to monitor people who present at the emergency room with symptoms of suspected ketoacidosis. A build-up of ketones can only occur when there is an absence of insulin in the body.
• Genetic testing may be performed to detect the specific gene mutation associated with MODY or NDM. In some cases, family members may also be tested to determine if they have inherited the same altered gene.
• Tests for other associated conditions, for example iron studies for suspected haemochromotosis.

Women who are diagnosed with gestational diabetes should be retested at 6-13 weeks after they have delivered their baby, to screen for persistent diabetes. This can be done with a fasting blood glucose or HbA1c.

While there is no way to prevent type 1 diabetes, the risk of having type 2 diabetes can be greatly decreased by losing excess weight, exercising and by eating a healthy diet with limited fat intake. By identifying prediabetes and making the necessary lifestyle changes to lower glucose, you may be able to prevent type 2 diabetes or delay its onset by several years. Normalising blood glucose can also minimise or prevent vascular and kidney damage.

There is currently no cure for type 1 diabetes. Transplantation such as islet (beta) cell transplantations and whole organ pancreas transports can potentially restore insulin production.

Diabetic treatment at the time of diagnosis is somewhat different than ongoing treatment. In diabetic ketoacidosis, with very high blood glucose levels, electrolytes out of balance, and dehydration affecting the function of the kidneys, hospital care with intravenous infusions of fluid, electrolytes and insulin is required.

Ongoing treatment of type 1 diabetes revolves around daily glucose monitoring and control with insulin, eating a healthy diet, and exercising regularly. The aim is to keep glucose as close to normal as possible.

When administering insulin, often the person must self-check their glucose levels and adjust their insulin dose before injecting themselves several times a day. Insulin pumps, programmable devices that are carried at the waist and provide small amounts of insulin (through a needle under the skin) throughout the day, are available for some and can more closely match normal insulin secretion. The amount and type of insulin administered must be adjusted to take into account what the person is eating, the size of their meals, and the amount of activity they are getting. There are several types of insulin available; some are fast-acting and short-lived while others take longer to act but have a longer duration.

If the glucose concentration goes too low (hypoglycemia) e.g. if too much insulin is injected, or food is not eaten as expected, or if their needs change unexpectedly (e.g. had to do more exercise than planned) glucose should be taken at the first signs. Therefore it is wise to carry glucose, in the form of tablets or sweets. Carrying glucagon injections (which stimulate the liver to release glucose) is also recommended for times when a person's hypoglycemia is not responding to oral glucose and someone else can give it if the person has become unconscious.

There is less need to self-check glucose in type 2 diabetes until people require treatments that can cause hypoglycaemia such as insulin. Initially, many people can control their glucose levels with diet and exercise, then a variety of oral and injectable medications are available until people require insulin injections.

The medications include drugs that:

• Stimulate the pancreas to produce more insulin
• Help make the body more sensitive to the insulin it is producing
• Slow the absorption of carbohydrates in the stomach (slowing down the post-meal increase in blood glucose)
• Block glucose from being reabsorbed from the urine by the kidneys
• Stimulate weight loss and/or satiety (sensation of being full so people eat less)

Diabetic ketoacidosis is much rarer in type 2 diabetes, as there is usually some endogenous (coming from the body) insulin production. However very high glucose concentrations in acute illness, or before diagnosis, can result in a similar picture with severe dehydration, kidney damage and coma.

Both type 1 and type 2 diabetes are associated with small vessel (microvascular) and large vessel (macrovascular complications). Microvascular complications include: diabetic retinopathy (eye damage), nephropathy (kidney damage) and neuropathy (nerve damage e.g. to feet). Macrovascular include coronary artery disease (leading to heart attacks), cerebrovascular disease (leading to strokes) and peripheral vascular disease (leading to claudication, ulcers and possible amputation). The metabolic syndrome caused by obesity in type 2 diabetes is an additional risk factor for developing the macrovascular complications. Good control of blood sugar will prevent or slow down the development of the microvascular complications. Good control of blood sugar but also of cardiovascular risk factors will help prevent the macrovascular complications e.g. blood pressure and cholesterol-lowering therapies.

With gestational diabetes, the mother-to-be will need to eat a modified diet, get regular exercise, and monitor glucose levels as often as her health practitioner suggests. If more control is needed, she will be given insulin injections, safest for the baby.

Usually, the diabetic state resolves after the birth of the baby, although the woman remains at a higher risk of developing type 2 diabetes and she should be carefully monitored with any subsequent pregnancies. Right after birth, her baby will be monitored for signs of low blood glucose (hypoglycemia) and for any trouble breathing (respiratory distress).

People who have underlying conditions, such as cystic fibrosis will need to be treated for these conditions, in addition to diabetes treatment. Otherwise diabetes treatment may be slightly different in some of the genetic types for example in which oral treatments may be more effective than usually expected.