C. WHAT IS DIABETES?
1 Definition
There are two types of diabetes- diabetes mellitus and diabetes insipidus. The type of diabetes we usually mean, when we use the word diabetes, is diabetes mellitus.
Diabetes is Latin for excessive production of urine and mellitus is Latin for “honeyed”, a result of the presence of abnormally high levels of glucose in the urine. Fortunately modern medicine no longer requires the physician to taste urine.
Diabetes is a life-long illness that may be associated with various complications including blindness, heart disease, kidney disease and damage to the feeling in the limbs (peripheral neuropathy). The Scottish Diabetes Survey 2001 revealed that approximately 2% of the Scottish population is recorded as having diabetes.
Diabetes is characterised by high blood sugar levels and disturbances of carbohydrate, fat and protein metabolism. These changes result from either an absolute lack of insulin or a relative deficiency in insulin action and/or insulin secretion.
Insulin is a hormone (messenger) that is produced by the islet cells of the pancreas. It passes into the blood where it circulates to all parts of the body. Insulin’s main action is to stimulate the various tissues of the body to “pick up food from the blood”. Without it the body “starves” regardless of how much is eaten.
2 Classification
Diabetes mellitus can occur on its own (primary diabetes mellitus) or as a result of another illness or disease (secondary diabetes mellitus).
Patients with primary diabetes mellitus are further classified according to whether there is an absolute lack of insulin being made (type 1) or whether there is a relative deficiency in insulin action and/or insulin secretion (type 2).
Patients with type 1 diabetes mellitus produce no insulin at all. They usually present with a relatively abrupt onset of severe symptoms, proneness to ketosis (acid production as a result of fat breakdown caused by “starvation”) and dependence on insulin injections to sustain life. The age of onset is usually but not always below thirty years. The diagnosis is usually made on the basis of symptoms and hyperglycaemia (high sugar levels in the blood).
Type 2 diabetes mellitus is more common. It results from a relative lack of insulin caused by both an increased insulin resistance (insulin is being made, often in large amounts but the tissues do not “recognise” it and therefore do not “pick up food from the blood”) and/ or reduced insulin secretion. Patients with type 2 diabetes mellitus are not dependent on insulin injections and are not prone to ketosis. They may require insulin to control high blood sugar levels if this cannot be managed with diet or oral hypoglycaemic agents (drugs that lower blood sugar levels by either encouraging the pancreas to make more insulin or making the tissues more sensitive to the insulin that is already there). The age of onset is usually, but not always, above forty years.
Impaired glucose tolerance is a category that can only be defined by the oral glucose tolerance test (see later). These patients do not have symptoms of hyperglycaemia and do not develop problems with their eyes, kidneys or nerves. They do, however, have the same increased risk of macrovascular complications such as myocardial infarction (heart attack) and cerebrovascular disease (stroke) as patients with diabetes mellitus. It is therefore not a “mild” condition.
Diabetes mellitus may occur in pregnancy when it is called gestational diabetes. If untreated there is an increased risk of babies being born larger than normal (macrosomia). These macrosomic babies often have difficulty controlling their own blood sugar levels when born and have to be carefully looked after. Most women with gestational diabetes return to normal after the baby is delivered although there is an increased risk of type 2 diabetes mellitus in later life.
Diabetes mellitus may also be a result of other illnesses or disease processes (secondary diabetes mellitus) such as malnutrition, diseases of the pancreas, other endocrine (hormonal) disorders (for example Cushing’s disease) and as a side-effect of drugs (for example steroids).
3 Biochemical Abnormalities
In type 1 diabetes mellitus there is a complete lack of insulin production by the pancreas. This lack of insulin results in decreased uptake of glucose by peripheral tissues particularly muscle and adipose (fat) tissue leading to a “catabolic state”. This means that the body thinks it is “starving” and therefore releases “stored food”. The muscles of the arms and legs and the liver release their stores of glucose (sugar) into the blood (glycolysis). This results in higher than normal levels of glucose in the blood. This excess glucose spills out of the kidney into the urine. Glucose tends to drag water with it and as a result large amounts of urine are produced leading to dehydration. Fat stores are also broken down and released into the blood (lipolysis). These high levels of fats include cholesterol (hyperlipidaemia), which can damage blood vessels. Fats in the blood are changed by the liver into a form of acid called ketone bodies. A high level of these fatty acids is called ketoacidosis, which can be a life-threatening condition. Excess ketone bodies in the blood will spill out of the kidney into the urine (ketonuria). In type 2 diabetes mellitus there is only a relative lack of insulin secretion and thus there is no break down of fat stores unless the patient induces starvation. As a result ketoacidosis does not occur.
4 Symptoms
Glucose tends to drag water with it and if large amounts of glucose end up in the urine then there will also be a lot of water lost. One of the early symptoms is therefore the production of large amounts of urine (polyuria) even though the body is dehydrated and would normally produce little in the way of urine. Frequent trips to the toilet at night often occur (nocturia). This loss of water from the body causes dehydration, which leads to increased thirst and the consumption of large amounts of fluids (polydipsia). High sugar levels also occur in the lens of the eye. The water that accompanies the high sugar levels makes the lens swell resulting in short-sightedness (myopia). High sugar levels in the urine also encourage the growth of candida leading to thrush of the genitalia.
If there is complete loss of insulin production the body starves and hunger is stimulated resulting in increased appetite and food intake (polyphagia). Despite this, weight loss occurs because of the lack of insulin. If ketoacidosis occurs high acid levels threaten to stop individual cells of the body from working. The body tries to compensate by “breathing away” the high levels of acid. This results in the classic sign of Kussmaul breathing (hyperventilation), where the patient breathes rapidly despite not being breathless. The breath of such patients is sweet from the presence of ketones. Untreated ketoacidosis can cause coma and death.
5 Diagnosis
DIABETES MELLITUS
The diagnosis of diabetes mellitus is based on blood sugar levels and symptoms. The criteria used are based on guidance from the World Health Organisation (WHO). A diagnosis of diabetes has important legal and medical implications for the patient. A diagnosis should never be made on the basis of urinalysis, BM testing or HbA1c measurement.
With Symptoms
In the presence of the typical symptoms of diabetes any of the following are diagnostic: a random venous plasma glucose concentration > 11.1mmol/l, a fasting plasma glucose concentration > 7.0mmol/l, a two hour plasma glucose concentration > 11.1mmol/l two hours after 75g anhydrous glucose in an oral glucose tolerance test (OGTT).
Without Symptoms
In the absence of symptoms, the diagnosis should not be based on a single blood glucose result. At least one additional glucose test result on another day with a value in the diabetic range is essential, either fasting, from a random sample or from the two hour post glucose load. If the fasting or random values are not diagnostic the two hour value should be used.
Impaired Glucose Tolerance (IGT)
This is a stage of impaired glucose regulation. The patient will not have any symptoms of diabetes. Diagnosis can only be made using an oral glucose tolerance test. Patients with impaired glucose tolerance have the same risk of macrovascular complications as people with diabetes. They are not at risk, however, of microvascular complications.
The initial fasting plasma glucose should be < 7.0mmol. The patient consumes 75g of glucose. Two hours later if the plasma glucose value is > 7.8mmol/l but < 11.1mmol/l then the patient has IGT. If the value is >11.1 the patient has diabetes and if <7.8 the patient is normal.
Impaired Fasting Glycaemia (IFG)
This has been introduced to classify individuals who have fasting glucose values above the normal range but below that diagnostic of diabetes. (Fasting plasma glucose > 6.1mmol/l but < 7.0mmol/l).
Diabetes UK has recommended that all those with IFG should have an OGTT to exclude the diagnosis of diabetes, and be actively managed with lifestyle advice.
Gestational Diabetes
This includes the groups formerly classified as gestational impaired glucose tolerance (GIGT) and gestational diabetes mellitus (GDM). As glucose tolerance changes with the duration of pregnancy, the gestation at which the diagnosis was made should be recorded and, if made in the third trimester, the clinician should be cautious about the clinical implication of impaired glucose.
Children
It should be noted that children usually present with severe symptoms and diagnosis should then be based on a single raised blood glucose result, as above. Immediate referral to a Paediatric Diabetes Team should always occur.
6 Epidemiology
Diabetes mellitus is endemic throughout the world. In 1992 it was estimated that six million people had type 1 diabetes mellitus. The incidence varied according to ethnic origin and geography with the highest incidence in Caucasian populations, particularly in Europe. In Finland there were more than 30 cases per year per 100,000 population whereas in Asia the incidence was far lower at 0.5 cases per year per 100,000 population (World Health Organisation 1994).
The first Scottish Diabetes Survey (Scottish Diabetes Survey Monitoring Group, 2001) was published by the Scottish Executive in November 2001. 16% were recorded as having type 1 diabetes. In addition to prevalence levels that are similar to those found in the Health Technology Board for Scotland (HTBS) survey, this survey gives age and sex distributions by NHS Board for the whole of Scotland. 53% of those registered were male. 22% were under 45 years, 33% were between 45 and 64, 24% between 65 and 74 and 21% were 75 or over.
The Audit Commission (2000) estimated that diabetes currently affects approximately 3% of the population in the UK and that this figure may double by 2010 as a result of obesity and an ageing population.
The Diabetes UK Campaign 2001 “Too many, too late”, stated that there are approximately 120,000 people who have been diagnosed with diabetes in Scotland and there could be as many as 90,000, as yet undiagnosed.1
The baseline survey carried out by HTBS suggests that the recorded prevalence of diabetes is approximately 2.5%. However, as the establishment of diabetes registers is now mandatory across Scotland, recorded prevalence is likely to increase with improved case ascertainment as has occurred elsewhere Grimshaw et al., (1999). Examples of this are seen in Lanarkshire, where the recorded prevalence of diabetes has risen from 2.0% to 2.8% in four years and in Tayside where prevalence has increased from 2.2% to 2.5% from 1991 to 2001.
Taking account of some under recording, if the true prevalence is 3% in the Scottish population (5,120,000); this implies that an estimated 153,600 people in Scotland have diabetes, i.e. approximately 150,000 people in Scotland have diabetes.
In Tayside the prevalence of Diabetes is 2.5% (0.3% type-1 and 2.2% type-2) and the annual incidence of diabetes is 0.24%. 25% are on diet alone, 50% are on tablets and 25% are on insulin (roughly half with type-2 and half with type-1 diabetes). 22% are known to have ischaemic heart disease, 7% have had strokes, 1% are “legally blind”, with an incidence of “legal blindness” of 0.03% per annum. 0.5% had endstage renal failure and 4.3% of patients died each year.
BLINDNESS DUE TO DIABETIC RETINOPATHY IN SCOTLAND
Cormack et al. (2001) have studied social work department blindness registration records in Fife from the period 1990-99 to identify those patients whose main diagnosis was diabetes. Of 2,529 people with diabetes, the mean number of blind registrations per year due to diabetes was 4.3 (95% confidence intervals (CI) 3.3 to 5.3).
At the end of December 1999, the prevalence of blindness due to diabetes was 210 per 100,000 diabetic population and the incidence of blindness due to diabetes was 64 per 100,000 diabetic population per year (95% CI 49 to 79 per 100,000 diabetic population per year)2 However, these are probably underestimates of the level of disease because the only source of legally recorded blindness in the UK comes from social work records. Also, patients may have mixed aetiology and diabetes may not be specifically identified. Furthermore, existing routine health service record systems do not reliably identify patients with diabetic eye disease or events associated with healthcare of diabetic eye disease. Consequently, special surveys or clinical audits are needed at present to identify the real burden of diabetic retinopathy and to link cases identified to previous screening histories. “The Report of the Certification and Registration Working Group” (Scottish Executive, 2001) summarises the start of an initiative that will improve the extent of blindness registrations. HTBS has written to this group to stress that the clear recording of underlying disease, particularly that of diabetes, should be carried out in the new scheme.
The Royal National Institute for the Blind (RNIB) Scotland (Consultation comment, 2002) has determined that in Scotland in 1996, approximately 35,000 people were registered blind or partially sighted. By determining prevalence by age group and applying this to the Scottish population they estimate that this figure should be nearer 87,000, i.e. the true figure for those who are blind or visually impaired may be more than double those actually registered. However, it is unclear whether those who are blind (as opposed to visually impaired) or those with diabetic retinopathy would be more likely to register. Even so, this seems to confirm that the data from Fife registration records2 will lead to an underestimate of those who are blind as a result of diabetes.
7 Vascular Complications
The complications of diabetes are mainly, but not entirely, vascular. Where large vessels are affected the complication is termed macrovascular and where small vessels are affected the complication is termed microvascular.
MACROVASCULAR
Myocardial infarction and cerebrovascular disease are twice as common in people with diabetes mellitus and peripheral vascular disease is four times as common. The usual protection for women from atherosclerosis before the menopause is also lost. Even after adjustment for smoking, hypertension and hyperlipidaemia, the risk of ischaemic heart disease is still higher in people with diabetes mellitus. Although metabolic control is clearly important in the pathogenesis of diabetic complications it is extremely difficult to eradicate the macrovascular complications as shown in people with impaired glucose tolerance. Although metabolic control is only “mildly” deranged there is the same risk of macrovascular complications as for people with diabetes mellitus.
MICROVASCULAR
Microvascular disease in diabetes mellitus causes nephropathy (kidney disease), peripheral neuropathy (impaired feeling in the limbs) and retinopathy. The kidneys of people with diabetes are vulnerable as damage to the capillaries in the glomeruli (tiny filters) can occur. The kidney’s function is to remove toxins from the blood stream by excreting them in the urine whilst at the same time not letting vital constituents escape into the urine. If not enough blood reaches the glomeruli to be filtered, the kidney responds by raising the blood pressure. This further damages the blood supply to the glomeruli and a vicious circle is entered. If the glomeruli do not work, too much protein may be lost and the body becomes fluid overloaded. More seriously, toxins that should be removed are not, eventually endangering the patient’s life. This high blood pressure also damages other blood vessels in the body such as the blood supply to the eye.
As well as commonly causing peripheral neuropathy, other forms of nerve damage may occur, including mononeuropathies, where single nerves that supply particular muscles may be damaged. This commonly affects the nerve supply to the eye muscles causing double vision or the nerve supply to the muscles of the hand causing impaired grip. The autonomic nervous system may also be affected causing a wide range of symptoms, such as silent myocardial infarction, impotence, postural hypotension (low blood pressure on standing causing dizziness and fainting), diarrhoea and small pupils that dilate poorly, if at all.
The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study clearly showed the importance of good metabolic control in preventing the development of these complications, especially retinopathy.
Diabetic neuropathy is the commonest microvascular complication of diabetes mellitus and with time affects 34-39% of patients with type 1 diabetes mellitus. Diabetic nephropathy eventually occurs in 30-40% of patients with type 1 diabetes mellitus. Incipient nephropathy, defined by a persistent increase in albumin excretion (microalbuminuria), is often accompanied by an increase in blood pressure and is also an independent risk factor for atherosclerosis. People with diabetes are seventeen times more prone to kidney disease and diabetes is now the leading cause of endstage renal disease (requiring dialysis) in the United States of America.
COMBINED COMPLICATIONS
Foot disease in people with diabetes is often a result of the combination of peripheral neuropathy and atherosclerosis. People with impaired feeling may not be aware of foot problems and may inadvertently wear poorly fitting shoes that damage their feet. People with diabetes are therefore advised to wear footwear at all times, to check their shoes regularly for ridges etc, not to ignore slight injuries, to avoid very hot baths and hot water bottles and never to self-treat corns or calluses.
8 Metabolic Management
The aim of the treatment in all types of diabetes is to keep the blood glucose level as normal as possible by administering insulin or by oral hypoglycaemic treatment or by dietary modification alone.
HOW ARE SUGAR LEVELS MONITORED?
Nowadays sugar levels are mainly monitored by checking the blood. The days of dipsticking the urine are largely gone. An important caveat is that if a person with type 1 diabetes feels unwell, or if their blood sugars are greater than 17mmols/l, then the urine should always be checked for ketones (ketonuria). If ketonuria is present this may indicate the start of ketoacidosis, needing prompt medical attention.
Nowadays, most patients test their blood sugar levels using a finger prick or an earlobe prick. When performing a finger prick sample it is important to ensure that the patient’s hands are clean (especially if sugary substances have been handled) and warm. This is also true if someone else on behalf of the patient is performing the test. A drop of blood should be allowed to fall onto the test strip rather than being smeared on. The sides of the last three fingers on the hand tend to be avoided, but more importantly the pads of the finger should only exceptionally be used. This is partly because the pads are one of the most sensitive parts of the body and also because if there is existing nerve damage from peripheral neuropathy then pricking the pads of the fingers may exacerbate it.
Apart from directly measuring the blood sugar level a more long term measure of blood glucose control can be made from measuring the percentage of red blood cells that have glycosylated haemoglobin (HBA1C). HBA1C is the stable product of nonenzymatic glycosylation of the beta chain of haemoglobin by plasma glucose and is formed at rates that increase with increasing plasma glucose levels. Red blood cells live for 120 days before they are replaced. By measuring the percentage of cells affected one can gain an idea of blood glucose control over the preceding two to three months.
In people taking insulin, ideally, blood sugars should be between 4 and 7 mmol/l before breakfast, before lunch and before tea. Before bed, the blood sugar should be between 7 and 9 to avoid nocturnal hypoglycaemia; (“4 is the floor”). This is not always possible as many people find that their daily lives are not predictable enough to run their control this tightly, without developing frequent hypoglycaemic episodes. As a consequence, many people with diabetes have to live with higher blood sugar levels than is ideal.
What Are The Consequences of Hyperglycaemia?
Hyperglycaemia is a medical term meaning that the blood sugar levels are abnormally high. This leads to dehydration.
Ketoacidosis
In patients with type 1 diabetes, hyperglycaemia may lead to ketoacidosis as previously explained. This may occur at the time of first presentation or may be due to an infection, myocardial infarction, stroke, omitting or taking too little insulin, surgery or trauma.
The symptoms of ketoacidosis include polyuria, polydipsia, lethargy/weakness, nausea/vomiting, abdominal colic and muscle cramps. The patient may also have sweet smelling breath from the ketones.
Treatment is by an infusion of insulin and fluids until blood sugar levels are stable, there is no ketonuria and blood urea, electrolytes and plasma osmolality return to normal.
What Are The Consequences of Hypoglycaemia?
Hypoglycaemia is a condition in which the blood glucose level is lower than normal (less than 3.5mmol/l). In reality, the symptoms of hypoglycaemia rarely occur until the blood glucose falls below 3mmol/l. Hypoglycaemic episodes (“hypos”) may be caused by too little food, missed or late meals, more exercise than usual (hypo occurs much later than exercise), too much insulin, alcohol, hot weather or injecting into a “fatty lump”.
Patients may experience some of the following symptoms: sweating, headaches early in the morning as a result of hypos during the night, lack of concentration, dizziness, unsteady gait, slurred speech and irrational behaviour.
Giving the affected person some quick acting carbohydrate followed by some longer acting carbohydrate so that the blood sugar levels do not immediately fall again is the mainstay of treatment.
If the person is conscious they should take 3 glucose sweets. These will raise blood glucose levels within a few minutes. This should be repeated if there is no improvement after 5-10 minutes. To prevent the blood glucose falling again, short acting carbohydrate should be followed by longer acting carbohydrate such as a carbohydrate snack, biscuit or fruit.
If the person is unconscious a thick glucose gel, “Hypostop” can be administered into the side of the mouth. This is absorbed through the cheek and does not need to be swallowed. In some cases intramuscular glucagon or intravenous glucose is required. Again, once the person is conscious, a longer acting form of carbohydrate must be given to prevent a recurrence of hypoglycaemia.
MEDICATION
The medication used for diabetes depends on whether the affected person is still producing any insulin. If no insulin is being produced, as in type 1 diabetes, then insulin must be given, as without it death will inevitably occur. If there is still insulin being made by the body then medication may not be required. In this situation initial management is usually by a three month trial of diet, followed by oral medication only if required. However, if oral medication is required but not sufficient to control the blood sugars, then insulin may be required.
Insulin
In type 1 diabetes, the patient is controlled on insulin and dietary therapy, which allows the sugar produced by the body to be used as energy. Presently, it can only be utilised by the body if given by injection. It comes from two sources- human insulin, which despite its name is made in a laboratory and does not come from people, and animal insulin, which is extracted from purified porcine (pig) pancreatic islet cells. In the past it was also manufactured from bovine (cow) pancreatic cells.
Types of Insulin:
- Short-Acting (clear) – Soluble insulin is injected subcutaneously (the fat layer just under the skin). It has a relatively rapid onset of action (30 to 60 minutes after injection). From the patient’s point of view this means that it should be taken 30 minutes before eating if it is to be most effective. Its peak action is 2 to 4 hours after injection with some activity for a further 4 hours giving a total duration of action of up to 8 hours. Human insulin tends to have a more rapid onset and a shorter overall duration than porcine insulin.
- Intermediate and Long Acting (cloudy) – When given by subcutaneous injection, intermediate- and long-acting insulins have an onset of action at approximately 1-2 hours, a maximal effect at 4-12 hours, and a duration of 16-35 hours. Some are given twice daily in conjunction with short-acting (soluble) insulin, and others are given once daily, particularly in elderly patients. They can be mixed with soluble insulin in the syringe, essentially retaining the properties of the two components, although there may be some blunting of the initial effect of the soluble insulin component (especially on mixing with protamine zinc insulin, see below).
- Human Insulin Analogues – The human insulin analogues, insulin lispro and insulin.htmart, have a faster onset and shorter duration of action than soluble insulin. Subcutaneous injection of insulin lispro or of insulin.htmart may prove convenient to those who wish to inject shortly before or, when necessary, shortly after a meal. They may also help those prone to pre-lunch hypoglycaemia and those who eat late in the evening and are prone to early nocturnal hypoglycaemia.
INJECTION TECHNIQUE
Insulin is given by subcutaneous injection with the needle inserted at right angles to the skin to it’s full depth either in the upper arms, upper thighs, the abdominal wall or the buttocks. Sites must be rotated on a regular basis to avoid fat hypertrophy that will lead to irregular release of insulin into the blood stream and unstable blood sugars.
TIMING OF INSULIN INJECTION
Insulin should be administered 30 minutes before a meal (except Humalog, which should be administered at or just after a meal). Once insulin has been administered food should always be taken to avoid a hypoglycaemic attack.
INSULIN STORAGE
Insulin can be kept at room temperature for up to one month. New vials should be stored in the door of the fridge. The insulin should never be allowed to freeze. Visual checks of the vial should be made and if crystals can be seen on the glass, the vial must be disposed of, as the insulin would be inefficient. For this reason never allow insulin to be stored in the hold of an aircraft.
Oral Hypoglycaemic Agents
Oral hypoglycaemic agents are drugs that lower blood sugar by making the body’s own insulin more effective. They are used in patients with type 2 diabetes where dietary therapy has failed. Dietary modification is still the mainstay of treatment for type 2 diabetes. Usually this involves a reduced calorie diet that is low in fat and refined carbohydrate and high in fibre. This should, in theory, slow down the rate of glucose absorption reducing the demand for insulin and reducing fat stores. Oral hypoglycaemic drugs can only be effective if the beta cells (found in the islets of Langerhans in the pancreas) are still able to produce some insulin. Oral hypoglycaemic agents belong to 5 main groups:
- Sulphonylureas – Sulphonylureas stimulate the pancreas to produce more insulin, which in turn, lowers blood glucose levels. This type of tablet is usually used for people who are of normal weight or underweight, as it may stimulate weight gain. Side effects are uncommon and usually mild. Occasionally, they can cause jaundice and allergic skin reactions. Rarely, more serious blood disorders occur. As sulphonylureas artificially stimulate insulin production it is possible for blood sugar levels to become too low, leading to the symptoms and signs of hypoglycaemia. This usually occurs if too many tablets have been taken or in the presence of excess alcohol consumption. Sulphonylurea induced hypoglycaemia may persist for many hours and must always be treated in hospital. Sulphonylureas should not be taken during pregnancy or whilst breast-feeding and insulin should be substituted. In general, insulin treatment is almost always required in medical and surgical emergencies. Examples of sulphonylureas include glipizide, gliclazide, glibenclamide, tolazamide and tolbutamide.
- Biguanides – The only available biguanide is metformin. It helps insulin to use glucose more effectively by reducing glucose production and making the tissues of the body more sensitive to the insulin that is already there. As it does not increase insulin production, it cannot lead to hypoglycaemia. It is usually used for people who are overweight, as it does not encourage weight gain. It frequently causes diarrhoea and abdominal pain and as a result should be taken with or after food. For this reason the dose should be built up slowly. Metformin can lead to a condition where there is too much of a particular acid circulating in the body (lactic acidosis). This usually occurs in patients with impaired kidneys and should not be used where even mild kidney impairment exists. Also, it should not be used in other situations associated with lactic acidosis such as severe dehydration, infection, shock, heart failure, respiratory failure, recent myocardial infarction, severe peripheral vascular disease, hepatic impairment and alcohol dependency. It is also not allowed in pregnancy and breastfeeding.
- Alpha Glucosidase Inhibitors – The only tablet in this group is Acarbose. It delays the rate at which sucrose (a form of sugar) and starch are digested. In turn, this slows down the rate at which the blood glucose level rises after eating. If a patient has an episode of hypoglycaemia whilst on Acarbose they must be given oral glucose and not sucrose. Acarbose, itself will not cause hypoglycaemia but may cause wind or soft, smelly stools. This latter side effect tends to subside with time.
- Insulin Sensitising Drugs – Drugs in this class include rosiglitazone and pioglitazone. They improve insulin sensitivity by acting on receptors in the liver and muscle. Since the majority of patients with type-2 diabetes are insulin resistant, reducing insulin resistance results in lower blood glucose and also may help to improve lipid profiles. Fluid retention and weight gain are the main side effects, but regular monitoring of liver function tests are also required.
- Postprandial Glycaemic Regulators – Drugs in this class include repaglinide and nateglinide. These drugs are rapidly absorbed and stimulate the betaislet cells in the pancreas to secrete insulin rapidly after a meal. Like the rapid acting insulin analogues, they try to mimic the normal physiological pattern, by lowering post-prandial hyperglycaemia (high blood sugars after meals), which is increasingly being recognised as an important risk factor for diabetic complications.