The Use of Clinical Biochemistry in the Management of Diabetes Mellitus
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Transcript of The Use of Clinical Biochemistry in the Management of Diabetes Mellitus
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The Use of Clinical
Biochemistry in the
Management of
Diabetes Mellitus
Su-Mei Tham
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Introduction
Clinical biochemistry is the branch of laboratory medicine in which chemical and
biochemical methods are applied to the study of disease. Biochemical investigations are
involved, to some extent, in every branch of clinical medicine. The results of biochemical
tests may be used for diagnosis and monitoring of diseases, to help decide treatment plans, as
well as assessing prognosis. They are also of some value in screening for diseases. However,
clinical biochemistry plays only a part in the overall assessment and management of the
patient. For some patients, biochemical analyses play a very small role in the diagnosis or
management of their condition, whereas for others, a diagnosis is made from the results of
certain biochemical tests only. Diabetes Mellitus is one such condition1.
The aim of this essay is to analyse the importance of biochemical testing in the management
of diabetes mellitus and its complications, including diabetic ketoacidosis (DKA) and
hyperosmolar non-ketotic (HONK) coma. It is important to understand how biochemical
testing is used in the management of diabetes, as the current cost of diabetes in the UK is 7%
of the total National Health Service budget. Patients with diabetes have a 10-30% reduction
in life expectancy and current poor glycaemic control in individuals has increased the use of
hospital beds six fold2. It is, therefore, very important to gain good glycaemic control, with
the use of biochemical tests, in order to reduce complications and their costs to the NHS.
I will also discuss the limitations of biochemical testing, including the areas where errors are
likely to occur and the future of point of care testing in the management of patients with
diabetes.
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Metabolic Disturbances in Type 1 and Type 2
Diabetes Mellitus
Metabolic disturbance Type 1 Type 2
Hyperglycaemia (resulting
in glycosuria)
Present Present
Dehydration Present Present
Polyuria Present Present
Polydipsia Present Present
Lipolysis and proteolysis Present (resulting in weight
loss)
Not present
Ketogenesis Present (resulting in
ketoacidosis)
Not present
Method
The best way to show the use of clinical biochemistry in the management of patients with
diabetes mellitus is to show it in clinical practice. I attended a diabetes clinic on two
occasions and saw, firsthand, how the results of biochemistry tests affected the management
of the patient. I have selected a patient from those that attended the clinic as an example of a
patient with well controlled diabetes.
My essay also hopes to show how biochemical tests are used in the management of DKA and
HONK patients. Whilst acting as the On-Duty Biochemist, my convenor came across both a
HONK and DKA patient, and I have included these patients in my clinical cases.
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Clinical Case 1
A patient with well controlled diabetes mellitus
A 75 year old female with type 2 diabetes (diagnosed 2001) attended the diabetes clinic for
her 6 month review. Complications of her diabetes include morbid obesity, hypertension,
hyperlipidaemia, ischaemic heart disease and cataracts. She is currently on metformin and
sitagliptin for her diabetes and simvastatin for her high cholesterol.
Blood tests were done on the day she attended for the clinic and the following biochemical
test results were obtained:
In the long-term management of diabetic patients, good glycaemic control is usually observed
by monitoring their HbA1c. A target HbA1c of less than 7% is recommended to reduce the risk
of vascular complications. Many patients require adjustment of their current therapy in order
to achieve this. Usually, if the patient is on insulin, their dose will be increased slowly over a
period of time in order to bring their HbA1c value down to below 7%. This patient is currently
taking metformin and sitagliptin for her diabetes, so in this instance, the patients dose of
metformin could be increased. However, because her HbA1c is close to 7%, it is unlikely her
medication dose will be increased, as this could be brought down through exercise andeducation on good diet alone.
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In type 2 diabetics, it is also important to monitor their weight, cholesterol and triglyceride
levels. This is because obesity is associated with increased risk of complications in type 2
diabetics. This is monitored by measuring the patients HDL and LDL levels. HDL is known
as protective cholesterol and LDL is harmful cholesterol, especially if deposited in
coronary arteries2. This is particularly important in this patients case, as she is already known
to have ischaemic heart disease which could be exacerbated by poor diabetic control.
It is common for diabetic patients to also have thyroid function tests when performing their
usual blood tests. This is because diabetes (type 1 or type 2) both have a degree of
autoimmunity involved in the pathogenesis of the disease. This may, therefore, increase the
patients likelihood of developing other autoimmune diseases, in particular thyroid diseases.
Hence, it is common practice to also order thyroid function tests along with the other blood
tests to aid early detection of such conditions3. In this patient, her results show raised TSH
levels, which will be monitored every time she attends the clinic, for further development.
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Lack of insulin also affects the bodys potassium balance. Insulin increases potassium uptake
by cells, so lack of insulin means potassium cannot be taken up, making the patient appear to
have normal or raised potassium levels in biochemical test results. The patient is in fact
hypokalaemic, as the potassium is excreted by the kidneys due to the osmotic diuresis.
Insulin, administered as part of their treatment (see below), stimulates potassium to be taken
up by the cells and the patient becomes hypokalaemic. This has dangerous consequences
owing to the effects of potassium on the heart and is considered in the treatment of DKA
patients with the intravenous infusion of potassium (see below)4.
Treatment
The treatment of DKA involves the administration of three agents1:
1. Fluids2. Insulin3. Potassium
It is very important to gain good venous access and document all fluids given, as the patients
saline is cut back as the patients fluid and electrolyte deficit improves.
The detailed management of a patient with DKA is shown below:
A Treatment Regime for Diabetic Ketoacidosis1
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Insulin is administered intravenously by an infusion pump, commencing initially at 6
units/hour. This dose is adjusted according to thepatients blood glucose levels, monitored
hourly at the bedside until it falls below 15 mmol/L. It is then monitored at 2-hourly intervals.
It is also recommended that the plasma glucose be confirmed by the lab every 2-4 hours.
Clinical Case 2
Diabetic Ketoacidosis
A 16 year old male, with an 8 year history of type 1 diabetes, was admitted to hospital with
persistent vomiting. He said he felt hot and sweaty, but denied any abdominal pain or
diarrhoea. He is currently on an insulin regime (Novomix 30) for his diabetes (62 units mane,
45 units nocte). On admission, his stats were as follows:
His biochemical test results on admission are shown below:
Temperature 35.9oC
Pulse 124/min
B/P 119/62
Respiratory rate 22/min
O2 SATs 100%
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Urinalysis Results
BLD NEG
PRO NEG
NIT NEG
KET +
GLU +++
pH 5
SG 1.015
LEU NEG
The diagnosis of DKA was made using the results of biochemical tests shown above. Typical
biochemical features of a DKA are shown in the table below5:
Biochemical Feature Notes
Hyperglycaemia This is shown by a markedly raised blood glucose level, almost 4
times that of the upper limit in this patients case.
Metabolic Acidosis This can be seen in the low bicarbonate levels. The breakdown of
ketone bodies releases hydrogen ions, causing the patient to
become acidotic. The body attempts to correct this shift in pH
with its natural buffering system, bicarbonate ions, which
combine with H+
ions to form carbonic acid. The carbonic acid
can then dissociate to water and carbon dioxide. Because of the
high H+ion concentration, the patients bicarbonate levels are
low.
Raised plasma andurine ketones
These levels are raised due to the -oxidation of fatty acids.Although both plasma and urine ketone levels should be raised,
this is not the case in this patient, who only has one + for ketones
in urine. This could be because the urine dipstick test used to
detect the ketones may give false negatives, due to the fact that
the test detects acetoacetate, but not -hydroxybutyrate. In the
early stages of DKA, more -hydroxybutyrate is produced than
acetoacetate (8:1 ratio), so urine ketone levels appear low. As the
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DKA is treated, -hydroxybutyrate is converted to acetoacetate
and the test becomes more positive.
Hyperkalaemia As mentioned earlier, lack of insulin causes potassium to be
released from cells, so the patient may appear hyperkalaemic ornormal. However, as insulin therapy is administered, the patient
can become quickly hypokalaemic, so potassium levels must be
monitored very closely and potassium replacement is often
required.
Raised plasma
creatinine and urea
This is due to dehydration, as osmotic diuresis occurs because an
increased blood glucose level exceeds that of the renal threshold.
Once DKA was diagnosed in this patient, the DKA pathway was commenced. Treatment of
this patient included intravenous access, administration of normal saline (0.9% solution)
and insulin infusion. Insulin was administered at an initial dose of 6 units per hour. Finger
prick glucose tests were carried out every hour and the dose adjusted accordingly:
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Venous blood samples were also sent to the laboratory for testing at intervals. The results are
shown below:
The principal aim of treatment of DKA patients is to correct the acidosis. This is more
important in terms of morbidity and mortality than correcting the hyperglycaemia5.
The patient made a full recovery.
Time (hours)
Normal range 1 6 21
Sodium (mmol/L) 136144 136 136 134
Potassium (mmol/L) 3.55.0 4.9 4.3 3.7
Bicarbonate (mmol/L) 2030 17
Urea (mmol/L) 2.37.5 8.2 6.7 2.9
Creatinine (mmol/L)
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Hyperosmolar Non-Ketotic Coma (HONK)
HONK is defined as the presence of hyperglycaemia without the marked hyperketonaemia
and acidosis seen in DKA5. It usually occurs in older patients, possibly because type 2
diabetes is associated with late onset. Patients are often dehydrated, as osmotic diuresis
occurs, resulting in reduced levels of consciousness.
The pathophysiology of HONK has many similarities to that of DKAthere is relative
insulin deficiency in the presence of excess catabolic hormone concentration. However, in
HONK, lipolysis and ketogenesis do not occur. The reason for this is unclear. It has been
suggested that the low circulating levels of insulin is just sufficient to prevent lipolysis, or
that the hyperosmolality found in HONK may have an inhibitory effect on lipolysis and
ketogenesis13
. Biochemistry test results, therefore, show some differences to that of a DKA
patients, as acidosis does not occur, (unless lactic acidosis develops).
Precipitating factors of a HONK include severe illness, dehydraton, certain drugs, e.g.
glucocorticoids and thiazide diuretics, myocardial infarction, stroke and infections5.
Treatment
Treatment of HONK patient is similar to that of DKA patients. The following agents must
be administered and the precipitating factor treated:
Agent Notes (comparison to DKA)
Fluids 0.45% saline (half-normal saline) is usually administered. Rehydration
should be slower in HONK patients than in DKA patients to avoid
neurological damage as a result of a rapid fall in plasma osmolality.
Insulin This is the same as in DKA patients. 6 units per hour is initially
administered and this dose is adjusted according to bedside monitoring of
blood glucose levels.
Potassium Potassium requirements in HONK patients is usually less than that of a
DKA patients as acidosis has not occurred.
Heparin HONK patients appear to have an increased risk of thromoboembolism, so
prophylactic heparin is also usually administered.
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Clinical Case 3
Hyperosmolar Non-Ketotic Coma
A 79 year old female was admitted to hospital with slurred speech and increasing confusion.
She has a history of anxiety, depression, chronic kidney disease, chronic confusion and
recurrent urinary tract infections, for which she has just finished a course of oral antibiotics.
She is currently taking metformin and gliclazide for her diabetes. Her stats on admission were
as follows:
Her biochemical test results on admission are shown below:
Temperature 36.4oC
Pulse 101/min
B/P 148/80
Respiratory rate 26/min
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Urinalysis results
BLD +
PRO +
NIT NEG
KET +
GLU +++
pH 5
SG 1.010
LEU NEG
The following biochemical features are typical of a HONK5:
Biochemical Feature Notes
Raised plasma creatinine
and urea
This occurs as a result of dehydration due to osmotic dieresis.
Hyperglycaemia Blood glucose levels rise as a direct result of lack of insulin.
Hyperosmolar plasma The plasma becomes hyperosmolar as water is lost due to
dieresis.Absence of ketones or
metabolic acidosis
Lipolysis does not occur so ketones are not produced and the
patient does not become acidotic.
Hypernatraemia
(only initially)
This is because there is increased cellular uptake of glucose and
water from the extra-cellular fluid, resulting in hypernatraemia.
This is usually corrected with treatment, but it may be necessary
to switch from an isotonic solution (i.e. normal saline) to a
hypotonic solution for rehydration. The sodium concentrationmust, therefore, be monitored very carefully to decide which
treatment is necessary.
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Treatment of this patient was with a similar treatment to the DKA patients. She was started
on a GKI regime Glucose, Potassium and Insulin. The glucose is given in the form of
10% dextrose solution with 2.0mmol of potassium chloride added to the solution and 10 units
of Actrapid insulin. This is an alternative management pathway. There is no evidence that
suggests the GKI regime has any benefit over the use of standard 0.45% saline solution6.
Bedside glucose testing allowed the patients blood glucose levels to be monitored and the
insulin dose altered accordingly:
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Venous blood samples were also sent to the laboratory at intervals and the results were as
follows:
Time (hours)
Normal range 12 36
Sodium (mmol/L) 136144 128 143
Potassium (mmol/L) 3.55.0 Unsuitable
for analysis
3.9
Urea (mmol/L) 2.37.5 9.6 3.5
Creatinine (mmol/L)
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Discussion
The use of biochemical tests in the diagnosis and monitoring of diabetes is both far and wide.
It is vital for the diagnosis of diabetes, but the diagnosis can only be made if the patients
present with the symptoms. There are still many cases of undetected, and untreated, diabetes
(approximately 850 000 in the UK7). It is not uncommon for a diagnosis of diabetes to be
made when the patient presents with a complication.
As mentioned earlier, HbA1c is also being studied as a potential diagnostic tool for diabetes.
HbA1c is currently being used only if other diagnostic tests are also carried out but maybe,
when more data and evidence is available, HbA1c could be used as a diagnostic tool in its own
right. This would be beneficial to the patient, as it means a period of fasting is not required. It
would also save time, as a blood sample can be taken as soon as a patient presents with the
symptoms of diabetes and a diagnosis could be made potentially within 24 hours.
Point-of-Care Testing
Point-of-care testing has been defined as any investigation carried out in a clinical setting or
the patients home for which the result is available without reference to a laboratory and
perhaps rapidly enough to affect patient management8. In diabetes, this could refer to the use
of glucose monitors in the long-term management of patients, or the use of machines, e.g.
ABG measurements, on the wards in acute complications.
The use of finger prick testing to monitor blood glucose levels is well established in diabetics.
Monitors, such as Accu-chek, were originally designed and marketed to be used by patients
in their homes so they can monitor their blood glucose levels before meals. This provides
them with an idea of when their blood glucose levels may be too high or low, e.g. before
meals or following exercise, so their insulin dose may be adjusted as their physician sees
necessary. However, recently, such monitors have been found being used in the clinical
setting without additional regulatory framework and limited training of their proper use from
staff. Some monitors account for possible errors from the user, e.g. some monitors warn when
a blood sample is inadequate, but there is still limited understanding among healthcare
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workers of their inaccuracy9. For this reason, it has been suggested that blood glucose levels
also be confirmed by the laboratories every 2-4 hours during treatment1.
Errors that are likely to occur on the wards can be classified as either human errors, or errors
of judgment. Human errors, such as poor specimen collection or an incompetent user, are
likely to produce inaccurate results. Errors of judgment include carrying out the wrong test,
or too many irrelevant tests. Regardless of the accuracy of the results produced, results are
irrelevant and hence, incur unnecessary costs. Both human error and errors of judgment can
be improved by training staff in the correct use of the equipment. This, however, is likely to
be costly and may still result in errors, leading to a quality issue.
Point-of-care testing was introduced to be both immediate and convenient, but it is important
for healthcare professionals to understand their limitations. Point-of-care testing on wards is
also likely to be costly when you consider the cost of the equipment and the cost of training
staff in their correct use. For these reasons, it is unlikely that the role of the biochemical
laboratory in the diagnosis and monitoring of diabetes mellitus will ever be diminished.
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References
1. Gaw A, Murphy MJ, Cowan RA, O'Reilly D St. J, Stewart MJ, Shepherd J. Clinical
Biochemistry: Churchill Livingstone, 2004. (Illustrated Colour Text).
2. British Heart Foundation. High Cholesterol http://www.bhf.org.uk/heart-
health/conditions/high-cholesterol.aspx(accessed 19th April 2011.
3. Patricia W. Thyroid Disease and Diabetes. Clinical Diabetes 2000;18(1):38 - 40.
4. Baynes JW, Dominiczak MH. Glucose Homeostasis, Fuel Metabolism, and Insulin. In:
Medical Biochemistry, 2nd ed.: Elsevier Mosby, 2005:273 - 97.
5. Smith J, Nattrass M. Hyperglycaemic Comas. In: Diabetes and Laboratory Medicine.
ACB Venture Publications, 2004:71 - 93.
6. Savage MW, Kilvert A. ABCD guidelines for the management of hyperglycaemic
emergencies in adults. Pract Diab Int2006;23(5):227-31.
7. Diabetes UK. What is diabetes?2009.http://www.diabetes.org.uk/Guide-to-
diabetes/Introduction-to-diabetes/What_is_diabetes/(accessed 17th April 2011.
8. Hobbs R. Near patient testing in primary care. BMJ 1996;312:263-4.
9. Pitkin AD, Coursin D, Rice MJ. Point of Care Devices Should Not Be Relied Upon for
Perioperative Glucose Measurement.Anesthesia & Analgesia 2011;112(1):247-8.
http://www.bhf.org.uk/heart-health/conditions/high-cholesterol.aspxhttp://www.bhf.org.uk/heart-health/conditions/high-cholesterol.aspxhttp://www.bhf.org.uk/heart-health/conditions/high-cholesterol.aspxhttp://www.diabetes.org.uk/Guide-to-diabetes/Introduction-to-diabetes/What_is_diabetes/http://www.diabetes.org.uk/Guide-to-diabetes/Introduction-to-diabetes/What_is_diabetes/http://www.diabetes.org.uk/Guide-to-diabetes/Introduction-to-diabetes/What_is_diabetes/http://www.diabetes.org.uk/Guide-to-diabetes/Introduction-to-diabetes/What_is_diabetes/http://www.diabetes.org.uk/Guide-to-diabetes/Introduction-to-diabetes/What_is_diabetes/http://www.diabetes.org.uk/Guide-to-diabetes/Introduction-to-diabetes/What_is_diabetes/http://www.bhf.org.uk/heart-health/conditions/high-cholesterol.aspxhttp://www.bhf.org.uk/heart-health/conditions/high-cholesterol.aspx