The Use of Clinical Biochemistry in the Management of Diabetes Mellitus

Su-Mei Tham

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-2- . biochemical analyses play a very small role in the diagnosis or management of their condition. in every branch of clinical medicine. It is. including the areas where errors are likely to occur and the future of point of care testing in the management of patients with diabetes. a diagnosis is made from the results of certain biochemical tests only. The aim of this essay is to analyse the importance of biochemical testing in the management of diabetes mellitus and its complications. For some patients. as well as assessing prognosis. whereas for others.Introduction Clinical biochemistry is the branch of laboratory medicine in which chemical and biochemical methods are applied to the study of disease. very important to gain good glycaemic control. to some extent. It is important to understand how biochemical testing is used in the management of diabetes. in order to reduce complications and their costs to the NHS. 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. including diabetic ketoacidosis (DKA) and hyperosmolar non-ketotic (HONK) coma. Diabetes Mellitus is one such condition1. The results of biochemical tests may be used for diagnosis and monitoring of diseases. They are also of some value in screening for diseases. with the use of biochemical tests. therefore. Biochemical investigations are involved. clinical biochemistry plays only a part in the overall assessment and management of the patient. However. as the current cost of diabetes in the UK is 7% of the total National Health Service budget. to help decide treatment plans. I will also discuss the limitations of biochemical testing.

I attended a diabetes clinic on two occasions and saw. Whilst acting as the On-Duty Biochemist. firsthand. my convenor came across both a HONK and DKA patient. -3- .Metabolic Disturbances in Type 1 and Type 2 Diabetes Mellitus Metabolic disturbance Hyperglycaemia (resulting in glycosuria) Dehydration Polyuria Polydipsia Lipolysis and proteolysis Type 1 Present Type 2 Present Present Present Present Present (resulting in weight loss) Present Present Present 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. and I have included these patients in my clinical cases. I have selected a patient from those that attended the clinic as an example of a patient with well controlled diabetes. how the results of biochemistry tests affected the management of the patient. My essay also hopes to show how biochemical tests are used in the management of DKA and HONK patients.

if the patient is on insulin. She is currently on metformin and sitagliptin for her diabetes and simvastatin for her high cholesterol. it is unlikely her medication dose will be increased. Usually. good glycaemic control is usually observed by monitoring their HbA1c. However. so in this instance. hypertension. ischaemic heart disease and cataracts. the patient‟s dose of metformin could be increased. hyperlipidaemia. 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. as this could be brought down through exercise and education on good diet alone. -4- .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. because her HbA1c is close to 7%. This patient is currently taking metformin and sitagliptin for her diabetes. their dose will be increased slowly over a period of time in order to bring their HbA1c value down to below 7%. 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.

-5- . This is because diabetes (type 1 or type 2) both have a degree of autoimmunity involved in the pathogenesis of the disease. This is because obesity is associated with increased risk of complications in type 2 diabetics. which will be monitored every time she attends the clinic. it is common practice to also order thyroid function tests along with the other blood tests to aid early detection of such conditions3. It is common for diabetic patients to also have thyroid function tests when performing their usual blood tests. in particular thyroid diseases.In type 2 diabetics. especially if deposited in coronary arteries2. This is particularly important in this patient‟s case. for further development. as she is already known to have ischaemic heart disease which could be exacerbated by poor diabetic control. In this patient. her results show raised TSH levels. increase the patient‟s likelihood of developing other autoimmune diseases. This is monitored by measuring the patient‟s HDL and LDL levels. Hence. This may. it is also important to monitor their weight. cholesterol and triglyceride levels. HDL is known as „protective‟ cholesterol and LDL is „harmful‟ cholesterol. therefore.

DKA and HONK are caused by sudden changes in the patient‟s metabolic state due to the lack of insulin. complications may occur.Complications of Diabetes Mellitus In some patients with poor glycaemic control. There are both acute and long-term complications associated with sustained periods of hyperglycaemia. The acute complications. These tests are. Diabetic Ketoacidosis (DKA) DKA is a medical emergency and the metabolic disturbances caused are the consequences of lack of insulin: The Pathophysiology of Diabetic Ketoacidosis4 -6- . essential in the management of diabetic patients presenting with acute complications. therefore. These changes are observable in the results of the patient‟s biochemical tests.

making the patient appear to have normal or raised potassium levels in biochemical test results. as the patient‟s saline is cut back as the patient‟s fluid and electrolyte deficit improves. administered as part of their treatment (see below). as the potassium is excreted by the kidneys due to the osmotic diuresis. Insulin 3. Potassium It is very important to gain good venous access and document all fluids given. Treatment The treatment of DKA involves the administration of three agents1: 1.Lack of insulin also affects the body‟s potassium balance. Insulin. Insulin increases potassium uptake by cells. stimulates potassium to be taken up by the cells and the patient becomes hypokalaemic. Fluids 2. The patient is in fact hypokalaemic. so lack of insulin means potassium cannot be taken up. 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. The detailed management of a patient with DKA is shown below: A Treatment Regime for Diabetic Ketoacidosis1 -7- .

with an 8 year history of type 1 diabetes. was admitted to hospital with persistent vomiting. He is currently on an insulin regime (Novomix 30) for his diabetes (62 units mane. commencing initially at 6 units/hour. his stats were as follows: 35. On admission. 45 units nocte). It is then monitored at 2-hourly intervals. Clinical Case 2 Diabetic Ketoacidosis A 16 year old male. He said he felt hot and sweaty.9oC 124/min 119/62 22/min 100% Temperature Pulse B/P Respiratory rate O2 SATs His biochemical test results on admission are shown below: -8- . but denied any abdominal pain or diarrhoea.Insulin is administered intravenously by an infusion pump. monitored hourly at the bedside until it falls below 15 mmol/L. This dose is adjusted according to the patient‟s blood glucose levels. It is also recommended that the plasma glucose be confirmed by the lab every 2-4 hours.

this is not the case in this patient. due to the fact that the test detects acetoacetate. In the early stages of DKA. As the -9- . Although both plasma and urine ketone levels should be raised. Raised plasma and urine ketones These levels are raised due to the β-oxidation of fatty acids. so urine ketone levels appear low. who only has one + for ketones in urine. more β-hydroxybutyrate is produced than acetoacetate (8:1 ratio). but not β-hydroxybutyrate. Typical biochemical features of a DKA are shown in the table below5: Biochemical Feature Hyperglycaemia Notes This is shown by a markedly raised blood glucose level. This could be because the urine dipstick test used to detect the ketones may give false negatives. Because of the high H+ ion concentration. bicarbonate ions. The carbonic acid can then dissociate to water and carbon dioxide.015 NEG The diagnosis of DKA was made using the results of biochemical tests shown above. causing the patient to become acidotic. The body attempts to correct this shift in pH with its natural buffering system. almost 4 times that of the upper limit in this patient‟s case. The breakdown of ketone bodies releases hydrogen ions. the patient‟s bicarbonate levels are low. which combine with H+ ions to form carbonic acid. Metabolic Acidosis This can be seen in the low bicarbonate levels.Urinalysis Results BLD PRO NIT KET GLU pH SG LEU NEG NEG NEG + +++ 5 1.

Raised plasma creatinine and urea This is due to dehydration. Once DKA was diagnosed in this patient. so the patient may appear hyperkalaemic or normal. β-hydroxybutyrate is converted to acetoacetate and the test becomes more positive. so potassium levels must be monitored very closely and potassium replacement is often required. the patient can become quickly hypokalaemic. administration of „normal‟ saline (0. as insulin therapy is administered. 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: -10- . Treatment of this patient included intravenous access. lack of insulin causes potassium to be released from cells. However. the „DKA pathway‟ was commenced.DKA is treated. as osmotic diuresis occurs because an increased blood glucose level exceeds that of the renal threshold. Hyperkalaemia As mentioned earlier.9% solution) and insulin infusion.

5 – 5. The results are shown below: Time (hours) Normal range Sodium (mmol/L) Potassium (mmol/L) Bicarbonate (mmol/L) Urea (mmol/L) Creatinine (mmol/L) Plasma glucose (mmol/L) 136 – 144 3. -11- .3 134 3.0 20 – 30 2.3 – 7.7 21 The principal aim of treatment of DKA patients is to correct the acidosis.2 101 23.0 1 136 4.7 79 2. This is more important in terms of morbidity and mortality than correcting the hyperglycaemia5. The patient made a full recovery.9 72 6 136 4.Venous blood samples were also sent to the laboratory for testing at intervals.9 17 8.5 <135 3.7 6.6 – 8.

certain drugs. Potassium Potassium requirements in HONK patients is usually less than that of a DKA patient‟s as acidosis has not occurred. Patients are often dehydrated.g. dehydraton. 6 units per hour is initially administered and this dose is adjusted according to bedside monitoring of blood glucose levels. e. The reason for this is unclear. It has been suggested that the low circulating levels of insulin is just sufficient to prevent lipolysis. It usually occurs in older patients. lipolysis and ketogenesis do not occur. Heparin HONK patients appear to have an increased risk of thromoboembolism. -12- . 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. The pathophysiology of HONK has many similarities to that of DKA – there is relative insulin deficiency in the presence of excess catabolic hormone concentration. in HONK. Treatment Treatment of HONK patient is similar to that of DKA patients. so prophylactic heparin is also usually administered. Insulin This is the same as in DKA patients. resulting in reduced levels of consciousness.45% saline („half-normal‟ saline) is usually administered.Hyperosmolar Non-Ketotic Coma (HONK) HONK is defined as the presence of hyperglycaemia without the marked hyperketonaemia and acidosis seen in DKA5. therefore. myocardial infarction. Precipitating factors of a HONK include severe illness. glucocorticoids and thiazide diuretics. (unless lactic acidosis develops). However. show some differences to that of a DKA patient‟s. as osmotic diuresis occurs. possibly because type 2 diabetes is associated with late onset. as acidosis does not occur. or that the hyperosmolality found in HONK may have an inhibitory effect on lipolysis and ketogenesis13. Biochemistry test results. stroke and infections5. The following agents must be administered and the precipitating factor treated: Agent Fluids Notes (comparison to DKA) 0.

4oC 101/min 148/80 26/min Her biochemical test results on admission are shown below: -13- . depression. for which she has just finished a course of oral antibiotics. Her stats on admission were as follows: Temperature Pulse B/P Respiratory rate 36.Clinical Case 3 Hyperosmolar Non-Ketotic Coma A 79 year old female was admitted to hospital with slurred speech and increasing confusion. She is currently taking metformin and gliclazide for her diabetes. chronic confusion and recurrent urinary tract infections. She has a history of anxiety. chronic kidney disease.

resulting in hypernatraemia. and urea Hyperglycaemia Hyperosmolar plasma Blood glucose levels rise as a direct result of lack of insulin. „normal‟ saline) to a hypotonic solution for rehydration. Absence of ketones or metabolic acidosis Hypernatraemia (only initially) Lipolysis does not occur so ketones are not produced and the patient does not become acidotic. but it may be necessary to switch from an isotonic solution (i. be monitored very carefully to decide which treatment is necessary. The plasma becomes hyperosmolar as water is lost due to dieresis.010 NEG The following biochemical features are typical of a HONK5: Biochemical Feature Notes Raised plasma creatinine This occurs as a result of dehydration due to osmotic dieresis. This is because there is increased cellular uptake of glucose and water from the extra-cellular fluid. The sodium concentration must.Urinalysis results BLD PRO NIT KET GLU pH SG LEU + + NEG + +++ 5 1. This is usually corrected with treatment. therefore.e. -14- .

Bedside glucose testing allowed the patient‟s blood glucose levels to be monitored and the insulin dose altered accordingly: -15- . Potassium and Insulin. There is no evidence that suggests the „GKI‟ regime has any benefit over the use of standard 0.45% saline solution6. She was started on a „GKI regime‟ – Glucose.0mmol of potassium chloride added to the solution and 10 units of Actrapid insulin. This is an alternative management pathway. The glucose is given in the form of 10% dextrose solution with 2.Treatment of this patient was with a similar treatment to the DKA patient‟s.

This is because acidosis is not likely to occur in HONK. The patient recovered from the HONK.5 <135 12 128 Unsuitable for analysis Urea (mmol/L) Creatinine (mmol/L) 9. -16- . Bicarbonate levels are also not monitored in this patient. It is recommended that blood glucose levels be measured in the laboratory as errors are more likely to occur in bedside monitoring (see Discussion). This is most likely because HONK patients are usually older at presentation than DKA patients and so are more likely to have other underlying disorders and complications. It is worth noting that there is a higher mortality rate associated with HONKs than with DKAs5.9 It is worth noting that in this instance.5 – 5. but unfortunately.3 – 7. due to other medical conditions.0 2.6 89 3. It is more important for bicarbonate levels to be monitored in DKA patients.5 60 36 143 3. the patient was later discharged for palliative care.Venous blood samples were also sent to the laboratory at intervals and the results were as follows: Time (hours) Normal range Sodium (mmol/L) Potassium (mmol/L) 136 – 144 3. glucose levels were not measured in the laboratory.

e. In diabetes.Discussion The use of biochemical tests in the diagnosis and monitoring of diabetes is both far and wide. It is not uncommon for a diagnosis of diabetes to be made when the patient presents with a complication. but the diagnosis can only be made if the patients present with the symptoms.g. This provides them with an idea of when their blood glucose levels may be too high or low. Point-of-Care Testing Point-of-care testing has been defined as “any investigation carried out in a clinical setting or the patient‟s home for which the result is available without reference to a laboratory and perhaps rapidly enough to affect patient management”8. As mentioned earlier. so their insulin dose may be adjusted as their physician sees necessary. e. ABG measurements. diabetes (approximately 850 000 in the UK7). such as Accu-chek®. However. before meals or following exercise. Monitors. It is vital for the diagnosis of diabetes. such monitors have been found being used in the clinical setting without additional regulatory framework and limited training of their proper use from staff. but there is still limited understanding among healthcare -17- . recently.g. HbA1c could be used as a diagnostic tool in its own right. on the wards in acute complications. e. when more data and evidence is available. as it means a period of fasting is not required.g. and untreated. There are still many cases of undetected. 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. HbA1c is also being studied as a potential diagnostic tool for diabetes. some monitors warn when a blood sample is inadequate. were originally designed and marketed to be used by patients in their homes so they can monitor their blood glucose levels before meals. HbA1c is currently being used only if other diagnostic tests are also carried out but maybe. It would also save time. The use of finger prick testing to monitor blood glucose levels is well established in diabetics. or the use of machines. Some monitors account for possible errors from the user. This would be beneficial to the patient. this could refer to the use of glucose monitors in the long-term management of patients.

however. or too many irrelevant tests. are likely to produce inaccurate results. For this reason. 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. is likely to be costly and may still result in errors. such as poor specimen collection or an incompetent user. Both human error and errors of judgment can be improved by training staff in the correct use of the equipment. Human errors. Errors that are likely to occur on the wards can be classified as either human errors. Point-of-care testing was introduced to be both immediate and convenient. For these reasons. results are irrelevant and hence. or errors of judgment. it is unlikely that the role of the biochemical laboratory in the diagnosis and monitoring of diabetes mellitus will ever be diminished. -18- . Errors of judgment include carrying out the wrong test.workers of their inaccuracy9. but it is important for healthcare professionals to understand their limitations. incur unnecessary costs. it has been suggested that blood glucose levels also be confirmed by the laboratories every 2-4 hours during treatment1. Regardless of the accuracy of the results produced. This. leading to a quality issue.

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