Diabetes: Questions and Answers
DIABETES
Diabetes Mellitus
The medical name for diabetes mellitus comes from the Greek word that means to siphon and the Latin word that means sweet like honey.
Diabetes mellitus is the name given to a group of conditions where there is too much glucose in the blood. It affects approximately 3% of the population. There are currently 1.4 million people with diabetes mellitus in the UK and it is expected that by 2010 that there will be a further 1 million. It costs the NHS 4.9 billion a year and affects a million people without them even knowing that they have it. (Devendra et al 2004)
RELATED BIOLOGY
Which organ is involved in the regulation of Blood Glucose Levels?
The pancreas.
Where is it located?
Retroperitoneally, within the curve of the duodenum and with the tail extending to the posterior surface of the spleen.
What type of tissue is it made up of?
Primarily glandular tissue that has both endocrine (Insulin) and exocrine (Pancreatic digestive enzymes) functions.
Which area of this organ is responsible for producing the hormones involved in the regulation of blood sugar levels?
The Islets of Langerhans
What are the main functions of insulin?
To reduce the levels of blood sugar by facilitating the uptake of glucose from the bloodstream into the cells.
It increases the rate of glycogen synthesis in the liver
It promotes the synthesis of fatty acids in the liver
It inhibits the breakdown of fatty acids in adipose tissue
It stimulates the uptake of amino acids
It increases cell permeability to potassium
(after Wills C et al 2003),
What type of substance is insulin made of? Circle the correct answer.
Carbohydrate Protein Fats
Name the calls that produce the hormone glucagon.
Alpha cells
What are the main functions of glucagon?
An insulin antagonist, it raises blood glucose levels by increasing hepatic glycogen breakdown.
It activates hepatic glyconeogenesis
It enhances lipolysis of triglycerides
One of these hormones has a Catabolic action and the other an Anabolic action.
State what these terms mean and identify which hormone falls into which category.
CATABOLIC
Catabolism is the breakdown of complex biological molecules into smaller component ones
Glucagon
ANABOLIC
Anabolism is the synthesis of complex biological molecules from simpler components.
Insulin
What are considered normal limits of blood sugar readings?
Fasting blood sugar 3.0 to 6.1 mmol/l (Client note: this is variable – I have quoted WHO figures – check what your tutor recommends and add it here!)
Those with levels of 6.1 to 7.0 mmom/l are said to have impaired glucose tolerance
(WHO 1985)
CLASSIFICATION OF DIABETES MELLITUS
State the 4 main categories.
To the client: this is a loaded question. There are many different classification schemes. I quote the categories as defined in RECD 1997
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Gestational diabetes mellitus
Secondary diabetes mellitus – includes:
Genetic defects of beta-cell function
Genetic defects in insulin action
Diseases of the exocrine pancreas
Pancreatitis
Trauma/pancreatectomy
Neoplasia
Cystic fibrosis
Hemochromatosis
Endocrinopathies
Acromegaly
Cushing’s syndrome
Glucagonoma
Pheochromocytoma
Hyperthyroidism
Somatostatinoma
Aldosteronoma
Drug- or chemical-induced
Vacor†
Pentamidine
Nicotinic acid
Glucocorticoids
Thyroid hormone
Diazoxide
Beta-adrenergic agonists
Thiazides
Phenytoin
Alfa-interferon
Infections
Congenital rubella
Cytomegalovirus
Uncommon forms of immune- mediated diabetes
Other genetic syndromes sometimes associated with diabetes
Down syndrome
Klinefelter’s syndrome
Turner’s syndrome
Wolfram syndrome
Friedreich’s ataxia
Huntington’s chorea
Lawrence-Moon Beidel syndrome
Myotonic dystrophy
Porphyria
Prader-Willi syndrome (RECD 1997)
Diabetes mellitus can be due to a deficiency in insulin synthesis, secretion and also in some cases resistance. It is also thought that some diabetics may have a combination of both.
State 5 causes of Primary Diabetes Mellitus [aetiology].
Primary Diabetes Mellitus is subdivided into Type 1 and Type 2 varieties
Aetiology of Type 1 is multifactorial. It is auto immune and trigger factors can be genetic or environmental
Environmental causes include exposure to Coxsackie B virus, Rubella virus and Cytomegalovirus and exposure to cows milk.
Aetiology of Type 2 is also multifactorial. It includes genetic factors and environmental factors including: western diet, lack of exercise, obesity and hypertension (Todd W et al 2000)
NB Causes are still unknown, the above are thought to be trigger factors.
State 4 causes of Secondary Diabetes Mellitus.
Causes of secondary Diabetes Mellitus. There are several types of secondary Diabetes Mellitus including:
gestational diabetes
malnutrition-related diabetes
pancreatic diseases causing diabetes
endocrine diseases causing diabetes
drugs and chemicals causing diabetes
genetic conditions causing diabetes
Causes depend on the variety but include pregnancy, pancreatitis and various drugs including:
steroids
thiazide diuretics
phenytoin
diazoxide
streptozotocin
Pancreatic diseases can cause Diabetes Mellitus including:
acute and chronic pancreatitis
pancreatic carcinoma
cystic fibrosis
haemochromatosis
Disease processes can also cause secondary Diabetes Mellitus including:
acromegaly
Cushing’s syndrome
glucagonoma
phaeochromocytoma
Complete the following chart by using the recommended textbooks to compare the two main types of Diabetes.
TYPE 1 TYPE 2
Age at onset juvenile (<25) adult (50+)
% of all cases about 10% about 90%
Acute/insidious acute insidious
Body build lean obese
Genetic link high low
Prone to ketoacidosis yes no
Autoimmune Disease yes no
Treatment insulin diet, oral hypog’s
(Harris M 1995).
What age group in the general population has the highest incidence of Type 2?
Typically the 55-75 age range (Harris M 1995).
Certain groups in the general population have an increased risk of developing Type 2 and currently Diabetes UK is promoting a campaign to identify those most at risk earlier, so that they do not develop the major complications associated with this chronic disease. This is called the Missing Million Campaign.
Names these “At Risk” Groups
1. History of Heart Disease
2. History of Stroke
3. Obese (BMI>30)
4. Over 50s
5. Over 40s if from African Caribbean or Asian backgrounds
PATHOPHYSIOLOGY / CLINICAL FEATURES
DEFINITIONS
Define the terms:–
Gluconeogensis
Biosynthesis of glucose from sources other than glycogen
Glycogenolysis
Oxidisation of hepatic glycogen into glucose
Briefly describe how insulin deficiency / absence can cause the above processes to occur.
Insulin deficiency and/or low glucose levels promote the secretion of glycogen
Glucagon promotes the activation of the enzyme adenylate cyclase in the liver which triggers glycogenolysis. This is exactly the opposite process to gluconeogenesis and is mediated by a number of enzymes, the most significant being pyruvate kinease
Clinical Presentation – Complete the following
When blood glucose levels arise above a certain amount the renal threshold in the kidneys is exceeded and glucose spills over in to the urine. This is called glycosuria. This excess glucose sucks up the water so that it can flow from the body; this is called. Large amounts of urine are excreted. This is called polyuria. Excessive thirst is called polydipsia.
Excessive urination can result in lowered blood pressure and shock. Blurred vision can be caused by fluctuations in the amount floaters and water in the lens of the eyes during periods of dehydration. This is called osmotic myopia of the lens. Cells are not able to access glucose so they do not receive any fuel and as a consequence cannot produce energy. This triggers the brain to send a message of hunger. This excessive hunger is called polyphagia. Lack of energy makes the individual feel tired and weak. Other sources of energy are sought. Fat stores are broken down to provide energy. This may result in ketosis. Breakdown of fats results in the production of ketone bodies which are excreted in the urine. These are acidic and alter the blood PH.
There is a sweet smell of ketones on the breath. This is called ketotic respirations. Weight loss also results. Breakdown of protein stores results in muscle wastage. Skin infections are common e.g. Staph boils, erysipelas . Excess glucose suppresses the natural defence mechanisms and the action of the lymphocyte* cells. Electrolyte imbalances occur. The electrolyte potassium affects cardiac muscle causing arrythmias if deficient. Urea and electrolyte imbalances also result in the following symptoms 1. Dry mouth 2. Thirst 3. Muscle weakness 4. Lethargy 5. Cardiac arrythmias.
Numbness and tingling in the feet and cramps may result from peripheral neuropathy.
Client Note (*)– this is debatable – your tutor may have a specific answer in mid for this one
The recommendations of the W.H.O “Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications” were formally adopted in the UK on the 1st June “2000. The key recommendation, with regard to diagnosis is that fasting plasma glucose should be lowered from 7.8mmol/L to 7mmol/L.
What is an OGTT?
The Oral Glucose Tolerance Test
In the oral glucose tolerance test the patient, after fasting for 15 hours, drinks 75 g of glucose in 300 ml of water, over 5 minutes. Blood glucose is measured before the drink and after 30, 60, 90 and 120 minutes. Urine is collected before the drink, and after 60 and 120 minutes. Before the test, for a period of 6 hours, the patient should avoid smoking and drinking coffee.
There is a normal glucose tolerance if the venous plasma value is less than 7 mmol/l after the 2 hour period,
If after 2 hours after the glucose load the value is between 7 and 11 mmol/l, then there is impaired glucose tolerance.
If glucose is greater than or equal to 11.1 mmol/l this is diagnostic of Diabetes Mellitus
OTHER TESTS / SCREENING PROCEDURES
What is an HbA1c Test and why is it carried out?
This is a measure of glycosylated haemoglobin in the blood. It is a longer term measure of the degree of blood glucose control. (DCCRG 1993)
NICE target is 6.5 – 7.5 HbA1c
When would Urea and Electrolyte levels and Blood Gases be tested?
Normally only if metabolic imbalance is suspected, dehydration, renal involvement or occasionally as a screen for end-organ pathology (kidneys). U’s + E’s may be requested as part of a monitoring procedure. Blood gases may be useful if severe ketoacidosis is present.
When would a Full blood count, specimen check and chest X-rays be carried out?
This is more likely to be done as a screening or monitoring procedure (FBC or Urinalysis) unless there was an obvious clinical reason for doing them such as suspected anaemia etc. A CXR would be less likely to be carried out unless pulmonary or cardiac pathology was suspected (Client: this is contentious – as different clinicians have different rationales for these investigations.)
When would and ECG and Lipid levels be checked?
ECGs are likely to be checked on diagnosis, as a monitoring procedure or if arrythmias have been detected. They may also be done as a baseline investigation, with hypertension or if cardiac involvement is suspected.
Lipids are very likely to be abnormal in Diabetes Mellitus. They would be checked as a monitoring investigation at most visits. (DCCRG 1993)
When would a neurological assessment and inspection of the lower limbs be carried out?
Peripheral neuropathy and vascular impairment are common sequelae to Diabetes Mellitus and this would be actively considered and evaluated at each monitoring visit. Probably at least twice a year or more frequently if indicated. (DCCRG 1993)
Why are protein levels checked?
Proteinuria is a good indicator of diabetic nephropathy. Urine protein should be checked at every monitoring appointment. Serum proteins are less sensitive but if renal pathology is established then it may be a useful investigation. (DCCRG 1993)
When is urine checked for ketones?
In the presence of dehydration, clinical suspicion of ketonuria, pregnancy and as a monitoring procedure. (DCCRG 1993)
When would an eye inspection / photography be carried out and why is this done?
Retinopathy is a potent cause of visual impairment and commonly found in the diabetic state. It is commoner with poorly controlled Diabetes Mellitus and Type I diabetes mellitus. It is one of a number of ophthalmic complications seen with diabetes and should be actively screened for at every routine visit. (DCCRG 1993)
Why would a diabetic require having their blood pressure regularly recorded and what value is recommended?
Hypertension is a common cardiovascular complication of Diabetes Mellitus and is an independent risk factor in Type II diabetes mellitus. The presence of hypertension and Diabetes Mellitus coexisting in the same patient will increase the overall morbidity risk of both cardiovascular disease and cerebro-vascular accident.
A blood pressure reading below 130/85 mmHg is an ideal goal for most people with diabetes who don’t have kidney complications, but some authorities may recommend an even lower blood pressure goal (below 120/75 mmHg) for people with diabetes who have kidney complications. (DCCRG 1995)
State the main complications
Short-Term
Hypoglycaemia, dizziness, lethargy, impaired conscious level – drowsiness.
Hyperglycaemia, nausea, headache, malaise, ketosis.
Coronary heart disease,
Cardiovascular disease (macro- & microvascular disease)
Retinopathy which can lead to blindness
Nephropathy, which can lead to kidney failure and the need for dialysis
Neuropathy which can lead to, among other things, ulceration of the foot requiring amputation
Microvascular
Retinopathy,
Nephropathy
Neuropathy
These are generally related to HbA1c levels with the highest incidence of complication occurring when HbA1c levels are above 12%
Atherosclerosis
Arteriosclerosis
Both processes can lead to :
heart disease
stroke
peripheral vascular disease
(Stratton I et al 2000)
What are the SIGN Guidelines and name those that relate to Diabetes.
A set of guidelines originally drawn up by Scottish Intercollegiate Guidelines Network. They include:
visual impairment (SIGN 4)
pregnancy (SIGN 9)
children and young people (SIGN 10)
renal disease (SIGN 11)
foot disease (SIGN 12)
cardiovascular disease (SIGN 19).
Treatment- Give Principles
Type 1
Always insulin dependent.
Active treatment involves titrating insulin dose against glucose levels and then maintaining levels by manipulation of the insulin regime
Constant monitoring by either patient or physician
Constant vigilance for complications
Type 2
Depends on cause, but in most cases treatment involves lifestyle modification, weight loss, dietary carbohydrate restriction.
If not successful then progression to oral hypoglycaemics and occasionally to insulin.
Constant monitoring for the presence of complications
Reduction of secondary causes of complication i.e. cessation of smoking.
INSULIN
Insulin was identified as a substance that prevented diabetes in the early 1890’s. Banting and Best extracted insulin from the pancreas of a dog in 1921 and the first human received a crude extract of insulin from the pancreatic glands of cattle in 1922. Over the years there have been many advances in the synthesis of insulin. Insulin is a protein. Insulin injections are vital for people with Type 1 diabetes as they are unable to produce insulin them selves and also for many with Type 2 diabetes whose condition has progressed to a point where tablets and diet cannot control it adequately. The aim of this treatment is to ensure that blood glucose levels are maintained at less that 6.5 mmol/l. (Client: see previous comments)
Name 4 factors which influence control
1. Weight
2. Severity of disease process
3. Diet
4. Level of exercise
(Wing RR, et al 2001)
There are a variety of insulins available on the market.
The two main sources are animal and human.
How is human insulin produced?
By recombinant DNA technology inserting human genes into bacteria such as E.coli which then produces insulin in commercial quantities.
The majority of diabetics are now on Human insulin but unfortunately some people are still required to take animal insulin. Many drug companies are wishing to phase out animal insulin and at present Diabetes UK is campaigning to maintain these.
Why does insulin have to be given by injection?
Being a protein it cannot be given by mouth as it would be denatured in the gastro-intestinal tract.
What other route is being researched as an alternative?
A great deal of research has been lavished on alternative modes of drug delivery.
Transdermal routes do not give reproducible and consistent blood levels.
Oral insulin has not been a possibility in the absence of a specific peptide carrier system that would work in the gut.
Nasal administration has been tried, but there was low bioavailability and absorption enhancers were needed, in addition the clinical effect was only over a very short period.
Pulmonary routes appear to be promising but we already know that the pulmonary route is comparatively inefficient and requires ten times the amount of insulin to achieve the same clinical effect.
Initial clinical trials show no side effects and research is currently continuing. (Heinemann L 2001)
SIDE EFFECTS
Initially on the commencement of insulin people may experience sensitivity around the injection site.
How would you recognise this?
This is a form of allergy.
It can be local, in which case the local skin becomes red and itchy at the injection site.
It may (rarely) be systemic giving rise to a uticarial reaction, tachycardia and tachypnoea. Very rarely a patient may experience anaphylaxis.
Symptoms of hypoglycaemia may occur if too much insulin is injected or if not enough carbohydrate is consumed or if there is increased exercise without taking extra food.
Hard lumps under the skin may occur at injection sites if they are not rotated.
What is the correct medical term for these?
Lipodystrophy
The number of units prescribed is calculated depending on time of day, age, weight and lifestyle.
Typical dose is 0.7-1.0 units per Kg of body weight.
WARNINGS
Insulin should never be administered in cases of HYPO.
The body may get used to low levels of blood glucose and therefore the warning signs for HYPOs are reduced. Individuals who have lost these may be advised to raise their blood glucose levels slightly for up to 3 months to resensitise themselves to symptoms. Some people have also found that they have lost some or all of their symptoms of HYPO when transferring from animal to human insulin.
Insulin dosages may have to change if there is disease of the adrenal pituitary and thyroid glands and also in the presence of liver and kidney disease. Taking of steroids will increase the insulin requirement.
During illness, puberty or emotional trauma glucose levels can become elevated and therefore insulin doses require to be adjusted and more regular blood sugar monitoring is essential.
During pregnancy insulin requirements may decrease in the first trimester and increase in the second and third trimester.
The following drugs may increase blood glucose levels and therefore lead to a need for more insulin –
Steroids
Contraceptives
Asthma Inhalers
Some drugs lower blood glucose levels and therefore result in a reduction in insulin. These are:-
Aspirin
Beta blockers
Mono-amine oxidase inhibitors.
There are four categories of insulin. Give an example of each.
Very short acting [ANALOGUE] – e.g. Humalog.
Short acting [SOLUBLE, NEUTRAL] – e.g. Actrapid, Human Velosulin.
Medium and long acting [ISOHANE, PROTAMINE ZINC] e.g. Human Insulotard.
Combination of short and medium acting [MIXED, BIPHASIC] e.g. Human Mixtard.
Who would most likely be prescribed very short acting insulins?
The very unstable or out of control diabetic. Children more likely than adults.
How long before a meal does short acting insulin require to be injected?
Depends on type. Sol. Insulin starts working within 30-60 mins and lasts about 6-8 hrs. Other types such as Insulin aspart and insulin lispro both start working within 15 minutes and last for up to five hours.
The glucose rise after a meal typically begins within about 15 mins so the insulin should ideally be in the system to counteract it.
How often daily would you require to take the following insulins:-
Short acting – about 2-4 times a day( when stable)
Medium acting – about twice a day
Long acting – Once (or perhaps twice) a day
These answers depend on the age and size of the patient, as well as the severity of the disease process.
Why is short acting insulin sometimes given with medium acting insulin?
To give a smoother blood glucose profile and also to “fill in the gap” before the medium acting insulin becomes biologically active.
Where should insulin be stored?
In the fridge, but not frozen.
Briefly discuss the types of equipment that are used to administer insulin?
Commonest is still the disposable insulin syringe. Syringe should always be calibrated to match the insulin type. Most are U-100 now.
Other options include the pen devices (expensive but convenient and largely “fool proof”).
Jet injectors are occasionally seen, but not very common.
In hospital surroundings insulin pumps (drivers or infusers) can be used.
Ambulatory subcutaneous pumps are increasingly used to deliver continuous infusion. Very expensive but arguably capable of producing the best control.
(HSG 1997)
What advice would you give to a diabetic who is planning to go abroad on holiday with regard to their insulin?
Take plenty with you as your brand may not be available abroad.
Make sure you can keep it refrigerated.
Run your blood glucose levels slightly higher than you are used to a) because of probable increased exercise and b) to reduce the risk of Hypo whilst away from home.
Be extra vigilant with the blood sugar monitoring. Strange diet may have unexpected consequences.
ORAL HYPOGYCAEMICS
Below are the main categories of drugs. Give an example of each, including daily dosage and side effects?
Sulphonylureas
Chlorpropamide
250 mg (100 mg in the elderly)
This is a very long acting drug, usually taken once daily with breakfast. Alcohol may cause flushing to the face.
Biguanides
Metformin
Start at 500 mg twice a day or 850 mg once daily. The maximum daily dose is 2550 mg given in three divided doses
Gastrointestinal side effects are a common occurrence in people taking metformin. Problems often include bloating, flatulence, nausea, stomach cramps and diarrhoea
Occasionally a metallic taste in the mouth. Rare complication lactic acidosis
(Knowler WC et al 2002)
Prandial glucose regulator
Repaglinide
0.5 to 4 mg with each meal
Occasional gastro intestinal side effects
(Bokvist K et al 1999)
Alpha glucosidase inhibitor
Acarbose
50 mg then titrated against clinical effect.
Flatulence soft stools or diarrhoea.
Glitazones [new drug]
Rosiglitazone
4mg as starting dose increasing to 8mg if required
Possible toxic effects on the liver (theoretical rather than practical)
(Park JY et al 2004)
ACUTE COMPLICATIONS
The most common is Hypoglycaemia. It results from an imbalance between glucose intake, endogenous glucose and glucose utilisation.
A decrease in the blood glucose level normally leads to stimulation of catecholamine secretion. Identify 5 causes.
Insufficient carbohydrate intake
Excessive carbohydrate utilisation (exercise)
Intercurrent acute illness
Overdose of insulin
Other illnesses (viz glycogen storage diseases)
Alcohol
Name 8 clinical features that the patient experiences.
Pallor
Shaking
Perspiration
Fatigue
A feeling of weakness
Rapid heartbeat (Tachycardia)
Hunger
Agitation
Difficulty concentrating
Irritability
Blurred vision
Temporary loss of consciousness
Confusion
Convulsions
Coma.
What would be given in order to treat it?
Depending on severity. If minor, warm sweet (glucose containing) drinks
If major, IM Glucagon. Monitoring essential until fully recovered.
What is ketoacidosis?
A clinical condition almost invariably associated with low insulin levels. As a result, the blood glucose levels rise and the intracellular glucose levels fall. This requires the metabolism at a cellular level to be fuelled with fat derivatives rather than carbohydrates and this produces acidic ketones. These ketones normally require the presence of insulin for their catabolism. In its absence, they build up causing a metabolic acidosis and spill over into the urine when the concentration is high enough.
Identify 5 causes
Fluctuations in insulin regime
Intercurrent illness
Trauma
Reduction in carbohydrate intake
Dehydration +- severe exercise
State 10 clinical features of this clinical state
High blood sugar levels
Frequent urination (polyuria) and thirst
Fatigue and lethargy
Dry skin
Facial flushing
Nausea
Vomiting
Abdominal pain
Fruity odour to breath
Rapid, deep breathing (Air hunger)
Muscle stiffness or aching
Coma
The principals of management are:-
Prompt administration of insulin (usually on a sliding scale) to reduce the hyperglycaemia and ketonaemia
Replacing fluid loss (from polyuria and vomiting) usually by intravenous fluids
Restabilising electrolyte imbalances secondary to dehydration, metabolic acidosis and hypokalaemia.
Treatment for any underlying cause such as infection.
LONG TERM COMPLICATIONS
There are 10 steps that the diabetic patient can take to reduce his chances of developing complications.
Regular screening of BP and maintain at 140/80 or lower.
Regular HbA1c testing.
Maintain blood glucose levels between 4-7mmols/L before meals.
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