Plasma Glucose (fasting Sample)
This is the "Gold standard" test for the diagnosis of Diabetes Mellitus (DM). The reference range for this test is between 4-6 mmol/l4,5. The patient's fasting blood glucose level, 12mmol/l, is far above the reference range confirming that he is suffering from DM. If they have not already been, urine ketone tests and serum Glutamic Acid Decarboxylase, islet cell and insulin antibody tests should be performed to rule out Type I DM and confirm the diagnosis of Type II DM6.
Urea
At 10.1 mmol/l his Urea levels are above the reference range, of 3.3 - 6.8 mmol/l 4,5. This could indicate impaired renal function, though could be the result of a high protein diet or recent surgery. It would be necessary to consider the patient's history and do further tests, such as creatinine levels to test his glomerular filtrate rate to test kidney function. Nephron damage (diabetic nephropathy) is often seen in DM patients with long term hyperglycaemia4, 5.
Haemoglobin A1C (HbA1C)
This is the key test to show whether a patient has been maintaining good glycaemic control. The test measures the level of glycated haemoglobin in the plasma and gives an indication of the longer term (6 weeks to 2 months) average level of blood glucose. The patients HbA1C is 10% which is above the reference range of <6.5% 4,5, indicating that he has been frequently hyperglycaemic over the past 2 months4.
Osmolality
This is a measure of the number of glucose, urea, sodium and potassium molecules/kg of serum. The patient's osmolality of 277mosm/kg is below the reference range of 285 -295 mosm/kg 4,5. The patient's serum glucose and urea levels are elevated, so we would expect to see a high rather than a low serum osmolality. This result could be due to test errors, loss of sodium because of diabetic osmotic diuresis, diabetic nephropathy or dilution of the blood by excess fluid consumption. It would be advisable to rerun the test to verify that the patient has low osmolality, before performing further tests to investigate the causes1, 4.
Conclusion
Based on his high glycated HbA1C percentage, the patient glycaemic control of his Type II DM is assessed as poor.
Question 2
Good glycaemic control is essential if the risk of diabetic complications is to be minimised2. There are acute short term complications of DM, such as hyperglycaemia and hypoglycaemia, and there are also long term chronic complications, such as kidney damage and blindness. Acute hyperglycaemia can lead to severe dehydration due to fluid loss from osmotic dieresis and hyperglycaemic coma which can be fatal. Hypoglycaemia can impair brain function due to neuroglycopenia, and can result in seizure and in severe cases death7.
As long as moderately good glycaemic control is maintained these potentially fatal consequences will be avoided. However there are also the longer term complications that require tighter glycaemic control if they are to be prevented from developing. For every 1% reduction in mean HBA1c there is a 21% reduction in long term complications8.
There are two categories of long term complication from DM; microvascular complications and macrovascular disease associated with atherosclerosis. Microvascular complications include nephropathy, neuropathy and retinopathy. If a patient can maintain their blood glucose level within an individual target range designed to avoid these longer term complications they are very likely to avoid the short term complications as well4.
Patients would often prefer to be a little hyperglycaemic than suffer the mild symptoms of hypoglycaemia such as anxiety, irritability, hunger and headaches. Therefore a balance must be struck between the short term effects of hypoglycaemia and the long term complications of hyperglycaemic. This balance will be dictated by the overall health of the patient and how they are affected by these symptoms of DM4.
Question 3
The patient believes that he has been tightly monitoring his glycaemic control, however the results of the HbA1C test would suggest otherwise. The first course of action would be to ensure that the patient fully understands the importance of good glycaemic control and how it can be achieved. This should help enable and motivate him to maintain good glycaemic control. It should be ensured that the patient is accurately monitoring his blood glucose at home and his monitoring device is working properly. He should monitor his blood glucose level atleast once a day for the next few weeks, to ensure that he is maintaining good glycaemic control4.
The next step would be to look at lifestyle factors, such as diet and exercise, as these have been shown to have a greater benefit than drugs9. If the patient is overweight, it should be recommended that he lose weight. The Pritikin diet and exercise programme could be suggested as it has been show to dramatically improve glycaemic control in patient after only a few weeks3. This involved eating less highly processed food and less simple sugars, and instead eating complex carbohydrates, lots of fibre and lean meat which release energy slowly. Exercise has been shown to reduce insulin resistance and improve glycaemic control4.
The patient's progress should be monitored at his next outpatient appointment. If the patient is not already taking medication to control his diabetes and lifestyle changes have not improved his glycaemic control it would be worth considering starting him on either insulin injections or a drug such as metaformin which increases the bodies sensitivity to insulin. The insulin could be delivered as a long acting injection given at night, with supplementary oral agents during the day9.
References
1. The American Association for clinical chemistry. Osmolality tests Reveiwed 12/04/2010. Viewed 20/04/2010. www.labtestsonline.org/understanding/analytes/osmolality/test.html#what
2. UKPDS Group, "Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes", Lancet 3 5 2 : 837-853, 1998
3. Frank W. Booth, "Physical activity and dietary intervention for chronic diseases: a quick fix after all?", J Appl Physiol 100: 1439-1440, 2006
4. G.Beckett, S. Walker, P. Rae and P. Ashby 2007. Lecture notes in Clinical Biochemistry. 8th edition. Pg 210 - 215
5. W.J. Marshal and S.K. Bangert. Clinical chemistry, sixth edition. Mosby Elsevier. Pg 92 - 98.
6. NICE, Type 1 diabetes: diagnosis and management of type 1 diabetes in adults, July 2004, viewed 20/04/01, http://www.nice.org.uk/nicemedia/live/10944/29391/29391.pdf
7. America Diabetes Association. Hyperglycermia. Copyright 2005. Viewed 20/04/2010. http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/hyperglycemia.html
8. Stratton et al. "Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study", BMJ. 2000 August 12; 321(7258): 405-412
9. Knowler et al. "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin", N Engl J Med. 2002 Feb 7; 346(6):393-403
Case study 2: Plasma triglycerides, cholesterol, HDL and LDL
Question 1
The patient's total cholesterol (12.6mmol/l) and LDL cholesterol (8.5mmol/l) are significant higher than the normal reference range (3.3-6.0mmol/l for total cholesterol and 1.8 - 5.0mmol/l for LDL cholesterol2). His triglyceride levels (2.3mmol/l) are marginally higher than the reference range (0.68 - 1.97mmol/l), while his HDL cholesterol levels (1.6mmol/l) are with the reference range (0.8 - 2.0mmol/l) 1,2.
This patient would be diagnosed with hypercholesterolaemia, as his total cholesterol levels are dramatically greater than the normal reference ranges described above 1, 2, 3, 4. The patient also has mild hypertriglycerideamia. Further differential diagnosis is difficult, as hypercholesterolaemia can be cause by a number of different conditions, such as:
Primary genetic factors (e.g. Familial Hypercholesteroaemia [FH] and Familial Combined Hyperlipidaemia [FCH]),
Secondary environmental factors (lifestyle e.g. diet),
A combination of genetic factors and environmental factors (e.g. Common Hypercholesteroaemia [CH]),
Secondary to other diseases (e.g. hypothyroidism or nephritic syndrome) 1,2,5.
Given his family history, FH and CH should be considered. FH is an autosomal dominant inherited disease present from childhood caused defective Apo B-100 lipoprotein and so limited LDL uptake and catabolism, leading to increased plasma LDL levels 1, 2. It is not dependant on the presence of environmental factors, though a poor life style can exacerbate it 2. FH is associated with total cholesterol levels greater than 7.5 mmol/l, plasma LDL level greater than 4.5mmol/l and tendon xanthomata 1,2,3,4. The patient fits this lipid profile and he should be checked for tendon xanthomata. CH is a disease where plasma cholesterol is significantly raised (though not usually as much as in FH). It is thought to be influenced by several genes and is also greatly influenced by environmental influences. FCH may also be considered, though this is an unlikely causes as the patients HDL levels are not low and there is only a small increase in the patients triglyceride levels 1,2.
Question 2
Raised LDL levels are a major risk factor in developing Chronic Heart Disease (CHD), as macrophages take up excess plasma LDL, leading to the formation of foam cells and atherosclerotic plaques which can result in myocardial infarction or stroke 3. Therefore raised plasma LDL levels must be reduced in primary and secondary prevention of CHD.
The preferred treatment to reduced plasma LDL cholesterol and triglyceride levels is through lifestyle changes. Numerous modifiable factors are associated with an increased risk of CHD, such as being overweight, having a poor diet, being inactivity/not exercising, smoking and drinking alcohol excessively 1,2,3,4. LDL cholesterol and triglyceride levels can be significantly reduced through lifestyle changes such as:
Eating a well balanced diet, that does not have excessive energy intake, no more than 30% of food consumed should be provided by fat, of which no more than a third should be saturated.
Exercising regularly
Losing weight by the above
Stopping smoking
Only drinking a moderate about of alcohol
Where FH is suspected, patients must be treated with lipid reducing medication e.g statins, as lifestyle factors are not the primary cause of the hypercholesterolaemia (though they can exacerbate it). Patients with Total cholesterol to HDL cholesterol ratios of greater than 6.0, other major risk factors for CHD (such as diabetes mellitus and hypertension), or high total CHD risk are also treated with such medication 3. Given the patients family history, his very high cholesterol levels, total cholesterol to HDL ratio of 7.9 and possible FH or CH, he must be treated with statins, as well as having his lifestyle assessed. Statins are hypolypidaemic agents which lower plasma by inhibiting the enzyme involved in cholesterol synthesis (hydroxymethylglutaryl CoA reductase). Reduced cholesterol production leads to reduced plasma cholesterol levels and so upregulation of LDL receptors leading to increased LDL clearance from the blood stream and further reduction in plasma LDL levels 1, 5.
Question 3.
Other considerations:
Other primary cause
It is important to ascertain that the hypercholesterolaemia is not secondary to another disease, such as hypothyroidism, diabetes mellitus, nephritic syndrome or cholestatis. Treatment with statins in these diseases would only treat the hypercholesterol symptoms and not the primary cause. 1,2,5. Hypothyroidism particularly shows a lipid profile similar to the patients, of a small increase in plasma triglyerides, a large increase in plasma LDLs, a normal HDL levels1.
Other risk factors
The patients total CHD risk should be calculated, which would take into account his age, sex, smoking status, systolic blood pressure, and total cholesterol to HDL ratio to give his percentage change of developing CHD over the next 10 years. This gives the doctor further information on which to decide upon treatments. If the patient is also overweight, smokes, drinks excessively, or has high blood pressure, then the doctor must explain to the patient the urgency in which he must change his lifestyle, and advise him how to do so. If the patient has high blood pressure may require treatment, for example with angiotensin-converting enzyme1,2,5. His GP may refer him for further advice and continuous lipid profile monitoring with a cardiovascular specialist.
Medication being taken
The GP must be informed of any medication the patient is takings, as some drugs can caused or exacerbate increased plasma cholesterol levels e.g thizides5.
Implication of the diagnosis on his family
As FH is suspected, this has implications to his family's health. Heterozygotes of FH have a severe symptoms. However if anyone in his family is a homozygote and is untreat, death can occur at a very young age. Members of his immediate and extended family of all ages should have their lipid profiles tested, so that hypercholesterolaemia can be identified and treated2.
