Type II Diabetes

Original article by Tom Leach | Last updated on 11/11/2014
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Aetiology

  • Underactivity, overeating and obesity are all factors in the formation of this disease.
  • It is thought that the presence of excess triglyceride within the cell has some effect in causing the insulin resistance.
  • The genetic link is type 2 diabetes is stronger than that in type 1 – monozygotic twins have a greater than 50% chance of developing the disease (compared to 30-50% in type 1).
  • MODY – maturity onset diabetes of the young – this is a rare type of type 2 diabetes. It will present in young people who have a family history of type 2 diabetes. It is dominantly inherited. The diabetes will be relatively easy to control.
  • There is evidence to suggest that low birth weight and low weight at 12 years of age predisposes to type two diabetes, as well as cardiovascular disease and hypertension. The theory is that low weight is related to malnutrition, and poor nutrition can impair beta cell development, thus putting you at greater risk of type 2 diabetes later in life.
  • There is no evidence that type 2 diabetes is related to autoimmunity. However, there is some evidence that inflammatory markers (CRP) and cytokines are raised in obesity, and as a result some people believe this plays a role in the development of diabetes.
  • Whether or not a person will develop type 2 diabetes is generally due to genetics. When it will occur is generally due to lifestyle.
  • Diabetes diagnosed in a man aged 40-59 will cause a reduction in life expectancy of 5-10 years. Therefore, preventing the onset of type 2 diabetes can have a significant impact on life expectancy. Diabetes diagnosed after the age of 70 has little effect on life expectancy.
 

Epidemiology

  • The four main determining factors are; age, obesity, family history and ethnicity.
  • The overall prevalence of this disease in the UK is about 2%. This rises to 10% by the age of 70.
  • The disease is relatively common in all populations enjoying an affluent lifestyle.
  • In poor countries, diabetes in a disease of the rich, but in rich countries, diabetes is a disease of the poor’
  • The disease may be present in a subclinical form for many years before it is detected.
  • The onset of the disease can be accelerated by stress, pregnancy, illness or certain drugs.
  • In western societies, adults of the age 25-55 gain about 1 gram of weight a day. This is due to an excess of just 90 calories a day (one chocolate coated digestive!), but is not due to overeating, more likely due to sedentary lifestyles.
  • The insulin resistant state associated with type two diabetes often presents with other risk factors that put someone at greater risk of cardiovascular disease. These include things like;      
  • Hypertension, obesity, hypertriglyceridaemia, decreased HDL cholesterol and acanthosis nigricans;
  • This is a condition where there is hyperpigmentation of the skin, particularly in the neck, axilla, groin and umbilicus. It results from excess insulin (which tends to be present in those with insulin resistance), which in turn causes excess growth of melanocytes. There are many causes of this, but the most common is type 2 diabetes.
  • The insulin resistant state, often combined with the symptoms above has been called syndrome X, metabolic syndrome, or insulin resistance syndrome.  The syndrome is basically a product of genetically susceptibility combined with a sedentary lifestyle, and obesity. It is not strictly a true syndrome, as alterations in the above factors can remove the aetiology, and thus mean you are no longer a sufferer of syndrome X.  Syndrome X is basically a state which puts you at much greater risk of cardiovascular disease and diabetes (i.e. you are on the road to developing these diseases), but by modifying lifestyle and body weight, you can ‘revert’ to being normal again.
  • About 1/3 of the adult population have some of these symptoms, not necessarily associated with type 2 diabetes.
  • Do not confuse this with ‘Cardiac syndrome X’.
 

Pathology

  • This involves a combination of insulin resistance and relative secretory failure of insulin. . Insulin is still released normally, and will still bind to its receptor, but it will not cause the normal physiological changes in a cell that you would normally expect. This occurs for reasons unknown. Type-2 diabetes results when a person cannot secrete enough insulin to overcome this ‘resistance’ factor. You have fewer beta cells (so they are under strain) trying to produce more insulin than a normal person requires.
  • Not only does this mean that there is a high blood glucose due to the fact you can’t remove normal digested glucose, but it has a secondary effect on the liver; there is less glucose entering liver cells, and so the liver reacts as if blood glucose were low, and begins glycogenolysis, and raises blood glucose even more.
  • Patients will have up to 50% of their beta cell mass at diagnosis. However, this destruction of beta cells is nowhere near as extensive as in type 1 diabetes. Most patients will also show amyloid deposition around the islets at autopsy. Amylin is a product secreted with insulin by the beta cells. it is not known if the amylin is a cause or a consequence of beta cell failure.
 
 
 

Diagnosing diabetes by glucose levels

This graph shows the development of type two diabetes in relation to insulin secretion and sensitivity.
At first there will be compensatory secretion of insulin to counteract the reduced insulin sensitivity, however as the disease develops more, the amount of insulin secreted will also reduce.
 
 
Often the same patient will show IGT and IFG. These stages are important because they show the first signs of the disease, and these patients should be followed up.
  • IGT – within 5 years, 25% of these patients will develop type 2 diabetes. 25% will also revert to normal glucose levels. Patients with IGT are not likely to suffer microvascular complications but can still suffer from cardiovascular disease secondary to IGT (macrovascular disease). These patients must be followed up due to their risk of developing macrovascular disease. So basically, the difference between diabetes and IGT is diabetes has microvascular complications, and IGT does not. However, there is the same high risk of macrovascular complications.
  • You should monitor these patients levels of glucose tolerance via an oral test.
  • Weight loss, increased physical activity, and a low fat diet have all been shown to reduce the risk of progression to type 2 diabetes. Currently, antihyperglycaemic drugs (e.g. metformin) are being evaluated for use in this group of patients.
  • IFG – almost identically to IGT, 25% of these patients will progress to type 2 diabetes within 5 years, and again, microvascular risks are thought to be negligible. However the cardiovascular risks are not as high as IGT or diabetes, but they are still increased over those of the general population.

Clinical presentation

  • Acute presentation – typically those with type 1, although not always
  • Usually young people. The history will be 2-6 weeks, and often consist of the classic triad of:
  • Polyuria – due to osmotic diuresis that occurs when blood glucose levels exceed the renal threshold. (the renal threshold is the concentration in the blood of a substance at which the kidneys will begin to remove it from the blood).
  • Thirst – due to the resulting loss of fluid and electrolytes
  • Weight loss – due to fluid depletion and the accelerated breakdown of fat and protein reserves as a result of insulin deficiency.
  • Ketonuria may also be present, and in severe cases it may progress to ketoacidosis.

Subacute presentation

The clinical onset is often very gradual over months or years. It is particularly common in older patients, and the older they are the more gradual the symptoms. There will be the same symptoms as present in the acute cases, but there may also be additional:
  • Lack of energy
  • Visual blurring – as a result of glucose affecting refraction
  • Inflammation of genitals (balanitis – inflammation of the glans penis in men, pruritis vulvae in females) – due to candida infection
Such cases may also present with complications:
  • Staphylococcal skin infections
  • Retinopathy – often noted during a visit to the optician
  • Polyneuropathy – causing tingling and numbness in the feet
  • Erectile dysfunction
  • Arterial disease – possibly resulting in MI, or gangrene.
 
Occasionally, hyperglycaemia or glycosuria may be detected incidentally (e.g. for insurance purposes). This is not diagnostic for diabetesAbout 1% of people have glycosuria naturally, due to a low renal threshold for glucose.
 

Diagnosis and investigations

If presenting symptoms are obvious, then further investigation (glucose level test) is not always necessary. However, the WHO states that for diabetes to be diagnosed, then you need symptoms of hyperglycaemia and a fasting glucose of above 7, or two separate glucose levels of above 7 (or above 11 if random and not fasting) . Note also that there are different thresholds for people in the middle (i.e. those with IGT and IFG) for microvascular and macrovascular complications; greater glucose levels are associated with higher risk of microvascular complications. The macrovascular complications occur at lower thresholds. 
  • The risk of macrovascular complications for those with IGT is the same as for those with diabetes.

IFG (impaired fasting glucose) is not as widely used as IGT. It also has a lower threshold for diagnosis, and thus more people fall into this category. Also, due to this lower threshold, the risk of macrovascular disease is not directly comparable to that of actual type 2 diabetes. Some people of course will fall into both IGT and IFG categories.

HbA1c and capillary glucose levels should not be used to diagnose diabetes.
For every person diagnosed with diabetes, there is another somewhere out there in the population who is undiagnosed.
  • The OGTT – oral glucose tolerance test – get the patient to fast overnight. In the morning give them 75g glucose in 300ml water, and take an oral sample before and two hours after the administration of glucose. This is the only test needed to diagnose diabetes.

Treatment

Education of patients is very important. This should take place soon after diagnosis. Patients should be informed of the benefits of good glycaemic control and how to stop signs of complications (such as diabetic foot). They should also be informed about reducing risk factors (e.g. stopping smoking!)

If accurate information is not supplied, then misinformation from friends and family may take its place.
Patients should be encouraged to learn how to manage their condition themselves, with guidance from clinicians.

  • 20-30% of patients can be managed by diet alone
  • About 1/3 of patients will be managed by oral treatments
  • About 1/3 will be managed with insulin

 
Step wise approach

  • Lifestyle
  • Lifestyle + metformin
  • Lifestyle + metformin + further drugs
  • Lifestyle + metformin + further drugs + insulin

 
When we talk about weight, we are particularly concerned with intra-abdominal weight as insulin resistance in closely linked to abdominal obesity. Measuring waist circumference is particularly important in identifying at risk populations. Weight is the most important factor for determining diabetes risk – the fatter you are, the greater the risk! – the risk rises exponentially!
 

Diet modifications

Dietary and lifestyle modifications can have a massive positive impact on insulin sensitivity.
Contrary to popular belief, the diet for somebody suffering from diabetes should be no different from a normal healthy diet. This should include:

  • A low sugar diet (although not sugar free)
  • High starchy carbohydrate (especially foods with a low glycaemic index). Carbohydrate should account for 40-60 of total energy intake.
  • Confectionary foods (cake biscuits etc) should account for no more than 10% of energy intake
  • Starchy carbohydrates are absorbed slowly and thus prevent rapid swings in circulating glucose. For example, the peak of circulating glucose is much lower than that seen when eating white potato.
  • High in fibre. Soluble fibre can be absorbed and has beneficial effects on metabolism. Insoluble fibre cannot be absorbed and so does not affect metabolism, however it is good for GI motility and increases feeling of satiety.
  • Low in fat (particularly saturated fat). Fat should not account for more than 35% of the energy intake
  • Low protein – this should account for no more than 10% of energy intake. Eating oily fish once or twice a week is recommended.
  • Vitamins and minerals – there is no evidence that supplements are beneficial, therefore these should be obtained through the mixed intake of fruit and vegetables in a well rounded diet.
  • Less than 6g salt a day. This should be even less in those with hypertension.
  • Alcohol is not forbidden but should be taken in moderation. Don’t forgets its calorific value, and also remember that it can cause hypoglycaemia in those treated with insulin.
  • Overweight people should be strongly encouraged to lose weight through dietary and lifestyle modification.

Generally, people find it very difficult to alter their diet. It may take many reminders. They should be encouraged to see a dietician. Changes to food intake should make as little impace on lifestyle as possible (i.e. don’t ask them to get all their food from a farm shop!).
 
In type two diabetes it is important that dietary and lifestyle modifications are attempted before tablet treatment. If these are adhered to, then the patient will see an improvement (if not complete control of) in the condition. This will prove to the patient that dietary modifications are of value in controlling their condition.
 

Sulphonureas

(e.g. tolbutamide, gliclazide)
These promote insulin secretion in response to glucose and other secretagogues.
They work by closing the K+ channels in the beta cell membrane thus causing opening of voltage controlled calcium channels, and allowing influx of calcium, which sets of second messenger cascades that result in the release of insulin by exocytosis.

  • They obviously require a certain mass of functional beta cells, otherwise they are ineffective. As a result they are not much use in ketoic patients. They should also e avoided during pregnancy.
  • They should also be avoided in those with liver conditions Some sulphonureas are removed primarily by the liver, whilst others are mainly removed by the kidney. Those with renal impairment should be placed on one which is primarily metabolised by the liver.
  • They encourage weight gain – and therefore should not be first line treatment in obese patients.
  • They interact with warfarin
  • They bind to albumin, and thus may be affected by other competitively binding drugs such as sulphonamides
  • Hypoglycaemia is a common side effect. It is also quite dangerous, because the effects of some of these drugs can last over 24 hours. In some cases this can mean hospitalisation is necessary.

Tolbutamide

  • This is the drug of choice in the elderly due to its short half-life. However, it is also less effective than other sulphureas.
  • It is largely metabolised by the liver, and can thus be used in cases of renal impairment

Glibencamide, glipizide, glimepiride

  • These are not suitable for use in renal impairment
  • They have a very long half-life and active metabolites

Gliclazide

  • Has a long half-life
  • Metabolised by the liver and thus can be used in renal impairment

Chlorpropamide

  • Very long half-life
  • Not suitable in renal impairment
  • very expensive (so not used in developing countries)
  • can cause a facial flush when used with alcohol
  • 1-2% will develop ADH like syndrome.

 

Meglitinides 

e.g. repaglinide, nateglinide

  • These are very similar to the sulphonureas, and act by the same mechanism – as insulin secretagogues.
  • Their receptor binding abilities are different to those of sulphonamides, and as a result they are very short acting and tend to promote insulin release around meal times – thus reducing the risk of hypoglycaemia.
  • They are more expensive than sulphonureas and their effectiveness as opposed to short acting sulphonureas has never been clinically assessed.

 

Biguanides 

e.g. Metformin.
Metformin is the only one of these.
This increases insulin sensitivity. The actual mechanism is unclear, but it reduces gluconeogenesis, and thus reduces glucose output from the liver, and so insulin sensitivity is increased.
This is generally preferred to suulphonureas because it cannot cause hypoglycaemia. Therefore this is normally first line treatment. However, in patients with a very low BMI, they may be given sulphonureas (as these encourage weight gain).
It is sometimes given in combination with sulphonureas or thiazolidinediones.

  • Side effects include ; epigastric pain, anorexia and diarrhoeaMany unnecessary colonoscopies have been ordered, when stopping metformin would have stopped the symptoms!
  • Metformin should not be used in cases of severe liver or kidney disease as lactic acidosis has been known to occur.  

 

Thiazolidinediones aka – GLITAZONES 

e.g. troglitazone The mechanism of these is not fully understood. They interact with a nuclear receptor PPR-gamma. This receptor is involved with genes that regulate lipid metabolism and insulin action. A popular theory as to how these work is that they lower the circulation of free fatty acids, and thus promote glucose utilisation by muscle cells.
These drugs will lower circulating insulin relative to glucose levels – i.e. they reduce insulin resistance – however,they will not return glucose levels to normal. As a result they tend to be used in combination with other agents.
It is important to monitor liver biochemistry, because they can cause problems with this.
They are generally used in patients who cannot tolerate metformin or sulphonureas.
They cause weight gain and salt retention.
 

Gliptins

These are relatively new drugs. They are involved with modifying the incretin effect. They bind to DPP-4 receptorsand thus inhibit these4 receptors. This causes a raise in the amount of GLP-1. This stands for glucagon-like-peptide, thus these peptides cause an increase in secretion of insulin from the pancreas, and reduce the amount of gluconeogenesis in the liver. This peptide is released by the presence of food in the stomach, and inhibiting DPP-4 reduces the activity of enzymes that break down GLP-1.
There are also treatments available that involve the direct administration of GLP’s, however, these are not as yet very effective, as GLP’s have an extremely short half-life (just a few minutes). These drugs are GLP-analogues and the most common one is Byetta. These more modern GLP analogues have overcome the short half-life problem and now last 2-4hours. The causes a feeling of fullness, and also reduce the amount of glucagon secreted.
 

Intestinal enzyme inhibitors 

e.g. acarbose
These inhibit the action of alpha-glucosidase. This is a novel way to treating overweight type 2 diabetes patients. These drugs will inhibit the breakdown of carbohydrates in the gut. Acarbose is a ‘fake’ sugar that will competitively bind alpha-glucosidase in the brush border. The result of this is that dietary carbohydrate is poorly absorbed and thus blood glucose levels to not rise as much.
This also means that undigested carbohydrate then carries on through the intestine, where it will be fermented, resulting in abdominal discomfort, flatulence and diarrhoea. These side effects can be minimised and even avoided through careful dosage management.
Orlistat also may have a role in weight management in diabetes. In inhibits intestinal lipase, and thus reduces fat absorption. It also induces steatorrhea which may have the secondary effect of reducing fat intake by the patient because the steatorrhea is unpleasant.
 

Insulin Treatment

Insulin is found in all vertebrates. There is very little variation in the molecule between species, and what variations there are only affect the antigenicity of the molecule, and do not affect its function in any way.
Short acting insulins
In some developing countries, synthetics insulins are still used, however in most developed countries these have now been replaced by synthetically produced varieties. This insulin is produced by genetically modifying yeast or bacteria to produce insulin.
Short acting insulins are the standard treatment for many patients. They are also used whenever continuous intravenous infusion may be needed, and in medical emergencies.

Normal insulin – This is not very useful in the short term. It tends to clog together in ‘hexamers’ which are 6 insulin molecules around a core of zinc. These will form soon after infusion, and prevent the insulin from ‘dissolving’ away from the initial injection site. This means that blood insulin levels don’t peak until 60-90 minutes after injection, and that their effect persists for too-long and can result in hypoglycaemia. Thus, insulins have been developed that have been slightly modified to prevent this effect. These are known as short acting insulin analogues. Analogues such asinsulin lispro and insulin aspart have been created, and with these, the insulin dissociates from the hexamers much more quickly, meaning it can diffuse away into the blood more easily, and also be removed from circulation more easily.
 
Long-acting insulins
To create this, you can add protamine or zinc to insulin, which makes it form crystals. Insulin prepared in this manner will be cloudy in appearance. You can alter the length of action of the insulin by:

  • Protamine – mixing protamine insulin with normal insulin – changing the ratio
  • Zinc – altering the size of the crystals formed.

You can also create longer acting insulin by making long-acting analogues that have had their structure altered.
 
Bi-phasic insulins
These can be made by mixing normal insulin and long-acting insulin together. This will give you a short burst of insulin to help you digest your meal, as well as giving you the benefits of long-acting insulins.
 
Inhaled insulin has recently been successful in clinical trials and is a very real alternative for the future. However, only short-acting insulins can be administered in this manner. With these preparations, you have to make as much insulin as possible reach the alveoli. The problem is that only 10% of the inhaled insulin reaches circulation, and this may have cost implications.
 
Administering insulin
This is usually done via a small needle. Often the injection is painless, but understandably patients are often apprehensive. The injection is normally given via a pen device into subcutaneous fat in the abdomen, thighs or arms. The needle should be inserted to its full length.
The injection site should be changed regularly to avoid lipohypertrophy
The rate of absorption of insulin into the blood depends on the site of injection, exercise, and warmth. It can also be speeded up by massaging the area. Absorption is most rapid from the abdomen, and slowest from the thigh.
 
In normal individuals, there is a sharp rise of insulin just after meals, superimposed on a background secretion level of insulin. In insulin treatment, we try to mimic this pattern. However, totally normal insulin levels are virtually impossible to achieve because;
Insulin secreted in the normal individual enters the portal circulation- and about 50% of it is cleared by the liver. Insulin given by subcutaneous injection is delivered to the systemic circulation.
Subcutaneous insulin takes up to 90 minutes to act – so its onset of action is too slow
Absorption of insulin is variable
It is very hard to achieve a basal rate of insulin secretion – the levels are constantly falling and rising in people who have to inject insulin, thus metabolic activity is altered from normal.
 
Multiple insulin regimens, with a longer-acting insulin before bed-time are recommended in younger patients. The provides great flexibility for meal times, and meal sizes – as the insulin peaks roughly with food intake. This is seen in example B above.
In type 1 diabetes there may be a ‘honeymoon period’ after insulin treatment is started, whereby endogenous insulin secretion returns, and thus insulin injections may have to be reduced or even stopped. However, this will only be a short respite. Strict control in type-1 patients will help prolong beta-cell life, and reduce the risk of hypoglycaemia.
Twice-daily injections require a stricter lifestyle. Mealtimes have to be fixed, and meal sizes also have to be roughly the same. These patients should aim for blood glucose of 4-7mmol/L before meals, and 4-10mmol/L after meals. This is seen in example A above.
 
In patients where hypoglycaemia is a problem, long-acting insulin analogues may be used. These are particularly useful in nocturnal hypoglycaemia. In normal insulin treatments, short-acting analogues are not used that often, as normal insulin is good enough in most cases.
 
Infusion devices are available in some regions. This is where a little gadget is attached to the patient and it delivers a constant trickle of subcutaneous insulin all day. A meal-sized dose can be delivered when the patient presses a button on the side of the device. They allow tailoring of insulin doses to meet a particular patient’s needs, e.g. they are good at preventing nocturnal hypoglycaemia. These have been extremely useful for some patients, but they are expensive, and many people will not like the fact they have to be constantly attached to a device. They are also a risk for infection.
 
Complications of insulin therapy
At the injection site – if the patient makes the injection too shallow, they can end up with a painful lesion, and there may even be scarring. Very rarely, abscesses form at the injection site.

  • Local allergic responses also occur at the injection site for some patients in early therapy. These tend to spontaneously resolve.
  • Lipohypertrophy – little fatty lumps – these may occur if one injection site is overused.

 
Insulin resistance – mild insulin resistance will cause obesity. In more sever cases, large doses of insulin may be needed. Some patients (those who poorly adhere) may require very large doses irregularly. Insulin resistance has been associated with antibodies against insulin receptors in patients with acanthosis nigricans.
 
Weight gain – many patients will experience this. The effect will be particularly apparent in patients who have had their dosage inappropriately increased – insulin makes you feel hungry! Generally it is the patients with the worst control who gain the most weight.
 

Experimental therapies

These tend to involve the pancreas. Whole pancreas transplantation has been attempted in patients who require kidney transplant – because they will already require immunosuppressive therapy; however, prognosis is not that great, and the immunosuppressive therapy is expensive and has many side-effects.
Another method has been to harvest beta-cell from cadavers, and inject them into the patient. These will adhere to the liver, and will function, however again these require immunosuppressive therapy.
 

Hypoglycaemia

This is defined as blood glucose of <3.5mmol/L. it occurs as a result of treatment and not as a result of diabetes itself. It usually occurs on those taking insulin, although it can occur in those taking sulphonureas, and rarely in those taking metformin.
Hypoglycaemia can sometimes occur in non-diabetic patients, in which case it is called spontaneous hypoglycaemia.
Symptoms of hypoglycaemia vary widely and differ with age. Sometime they can be vague, such as tiredness, irritability (possibly anger) and general behavioural changes (particularly in children) .
Common symptoms include: Autonomic:

  • Sweating
  • Trembling
  • Pounding heart
  • Hunger
  • Anxiety

Neuroglycopenic (due to lack of glucose to the brain)

  • Confusion
  • Drowsyness
  • Speech difficulties
  • Inability to concentrate
  • Inco-ordination

Non-specific

 
In many cases of hypoglycaemia, the patient can recognise the symptoms and take appropriate action. If they are asleep, lying down, or distracted by another activity, they may not recognise the event as easily. However, there are also two more important factors that affect recognition of hypoglycaemia:
Impaired perception of hypoglycaemia – in people without diabetes, symptoms of glycaemia will be present if blood glucose drops below 2.5-3.0mmol/L. in diabetic patients who are chronically hyperglycaemic, the same effect may be seen with higher levels of blood glucose. However, the real problems are in people with ‘very well controlled diabetes’ partciulalry those on insulin. They may be so used to low blood sugar levels, that symptoms do not really show themselves, even well below the 2.5mmol/L level. However, the effects of hypoglycaemia are still present, even if the symptoms are not – i.e. they are more likely to slip into a coma without realising they are having a hypo. Patients are 6x a likely to have a hypo in this situation.

  • In insulin treated patients, this effect is irreversible once it has occurred. After 20 years of insulin treatment, almost 50% of type 1 diabetes sufferers are affected.
  • In therapy treated patients, the effect is thought to be reversible.

Therefore it is important to note the importance of controlling glucose levels within certain limits – not just trying to get it down as low as possible.
Deficient counter-regulatory mechanisms – in an individual without diabetes, when the blood glucose beings to drop, glucagon and adrenaline may be released. These are the two most powerful hormones at keeping blood glucose up.
Within 5 years of type 1 diabetes developing, the hypoglycaemia – glucagon action will be impaired in most patients. After several years, many may also develop impaired adrenaline response in relation to glucose.
Both mechanisms described above often happen in conjunction, suggesting a similar pathological mechanism in the brain that accounts for both.
 
Causes

  • Missed, delayed or inadequate meal
  • Alcohol
  • Exercise
  • Breastfeeding by diabetic mother
  • Poor adherence
  • Badly designed insulin regimen

 
Risk Factors – many of these will be obvious if you have read above!

  • Sleep
  • Previous hypoglycaemia
  • Age (very old and very young)
  • Strict control of diabetes
  • Duration of diabetes
  • Renal impairment

 
Hypoglycaemia is serious! Sever hypoglycaemia (which is any glycaemia that requires another person to help the individual recover) has a mortality of 2-4%.
Occasional, death whilst asleep can occur in otherwise well diabetes type 1 patients. It often occurs in the young, and is known as ‘dead in bed syndrome’. It is though this is caused by a hypoglycaemia induced cardiac arrhythmia, or respiratory arrest.
During the night, the level of blood glucose fluctuates naturally. During the early hours of the morning it is quite low, but then rises by about 4am. This means that many patients on insulin wake with a high blood glucose. This can be reduced by taking more insulin before bed, however, this increases the risk of hypoglycaemia during the early hours of the morning. Patients are therefore recommended to take a higher amount of insulin, and also have a bedtime snack.
 

Managing Hypoglycaemia

Mild attack – patients should always carry readily absorbed carbohydrate in the form of glucose or sweets. In more severe cases, liquid carbohydrate (such as Lucozade) is more effective. Patients and close relatives need appropriate training about hypoglycaemia. Patients should not take more carbohydrate than necessary, as this increases the risk of rebound hyperglycaemia. Patients should also be warned about alcohol excess and the dangers of driving.
Severe attack – this is where severely impaired consciousness or even coma occurs. Often the diagnosis is quite simple and can be made clinically. This may be aided by a blood test if you are unsure. The diagnosis may also be aided if the patient carries a card or wears a bracelet stating that they are a diabetic. Patients should be given intramuscular glucagon or intravenous glucose (this will be 50% dextrose, and give 25-50ml). The intravenous glucose should always be followed by a saline flush, as dextrose causes sclerosis of veins. Glucagon acts almost as rapidly as glucose in increasing the blood level of glucose – however, remember that it will not work after a prolonged fast, and once the patient is revived, you should give glucose anyway to replace glycogen reserves.

  • Often many patient carry a glucagon pen with them, and can administer it themselves or have a relative do it in the case of a severe attack.
  • Oral glucose is always the first option – further treatments should only be considered if this is not possible (i.e. the patient is not able to swallow due to impaired consciousness).

Following recovery it is important to try and identify a cause, and make adjustments to the insulin regimen to reduce the risk of further hypoglycaemia. The general rule is to reduce the next dose of insulin by 10-20% until medical advice can be obtained.
Exercise can also induce hypoglycaemia – due to fact that during exercise, your body would normally naturally reduce the amount of insulin secreted – but in insulin controlled patients, this doesn’t happen. If patients anticipate they are going to be involved in strenuous activities, they should decrease their insulin dose, and increase carbohydrate. They should make doubly sure there is a supply of glucose ready incase of hypo.
 
Nocturnal hypoglycaemia
This often goes undetected, and thus actual figures for how prevalent it is are difficult to obtain. Some symptoms of this may be ; poor quality of sleep, morning headaches (‘hangover feeling’), chronic fatigue, and vivid dreams or nightmares. There may also be profuse sweating.
 
Hypoglycaemia is linked to a reduced risk of complications. The better your control (of diabetes) the more likely you are to have hypo’s, however, the less likely you are to suffer complications. Thus, you can say that more frequent hypo’s means fewer complications.