Diagnostic Tests of Diabetes Mellitus

Biochemistry 404,489 Views

Diabetes Mellitus is categorized by disorders of carbohydrate, protein and fat metabolism. Diagnostic tests are numerous, most of them are given below

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Urine “Glucose”

– lacks sensitivity = positivity in disease

– poor specificity = negativity in health

• Problems

– renal threshold variable 6 to 15 mmol/L

– interferences : Clinitest / Glucose oxidase strips

If urine test positive a confirmatory blood test is needed

Blood Tests

• Glucose

– whole blood 10-15% lower than plasma

– venous 10% lower than capillary

– Preservatives not 100% effective

• heparin / serum – loss of 1 mmol/L per 2 hours

• fluoride / oxalate – loss of about 10% overnight

• Insulin / glycosylated Hb / fructosamine

– No use for diagnosis

Diagnostic Criteria

• Plasma glucose :

A) Symptoms + random value > 11.1 mmol/L

B) Fasting value > 7.0 mmol/L

C) 2-h post glucose load (75g) value > 11.1 mmol/L

If one of these criteria is met then repeat testing the following day is required for confirmation

Oral Glucose Tolerance Test (OGTT)

• Complicated test no longer recommended for routine use except in pregnancy

• Still available in many laboratories

• Still found in text books

• Used in testing in pregnancy

• This evaluates the endogenous insulin response to a physiological glucose challenge

• The diagnostic value of OGTT has been over estimated and is used too frequently in situations where it is not needed

• In the absence of a specific marker of the diabetic state the OGTT remains the most sensitive and practical test for the early recognition of asymptomatic diabetes, without fasting hyperglycaemia even if it is a non-specific test.

Indications of OGTT

• Evaluation of a person with a borderline elevation of fasting or post prandial plasma glucose

• Diagnosis of gestational D.M

• High risk individuals

• Evaluation of glycosuria

• Assessment of unexplained presence of what might be expected a diabetic complication e.g. Neuropahty

• Metabolic condition (elevated triglycerides)

• Obesity

• Clinical or epidemiological research projects

Preparation Of Patient For OGTT

• The patient must be ambulatory and free from pyrexia, acute illness or trauma for at least two weeks.

• He/she should have diet containing at least 150 g carbohyrate per day for three days prior to test

• Any drug that alter blood glucose level should also be discontinued prior to testing for 03 days.

• The test should be done in the morning

• The patient must have 8 – 16 h fast.

• Heavy tea and coffee drinkers should reduce their consumption

• Smoking should be avoided

• No physical exercise or activity is allowed

• Patient should be seated quietly and relaxed for 30 minute for test

Procedure For OGTT

• Glucose load

– For adults 75 g glucose

– For children 1.75 g/kg body weight

– Glucose load is given in water (25 g/dl)

• This blood samples are taken at half hourly interval up to 2 hours

• Urine samples are usually not required for the diagnosis of diabetes mellitus

Interpretation Of OGTT

• Normal

– Fasting < 5.5 mmol/l

– 0.5, 1.0, 1.5 hrs < 10 mmol/l

– 2 hrs sample < 7.8 mmol/l

• Diabetic

– Fasting > 7.8 mmol/l

– 2 hours or one intermediate

– Sample > 11.1 mmol/l

• Impaired OGTT

– Fasting < 5.5-7.8 mmol/l

– One intermediate sample > 11.1 mmol/l

– 2 hrs between 7.8 and 11.1 mmol/l

OGTT In Gestational D.M

• OGTT is done with a glucose load of 100g

• Blood samples are taken up to 3 hrs, at least two values must exceed the following

fasting 5.8 mmol/l

1 hr 10.5 mmol/l

2 hrs 8.6 mmol/l

3 hrs 7.8 mmol/l

Fasting Plasma Glucose

• Reference range for plasma glucose for venous blood sample (3.3-5.5 mmol/l) – 60-100 mg/dl

• Duration of fast 10-14 hrs

• It is a specific screening test

• Glucose value > 7.8 mmol/l (140 mg/dl) is diagnostic

• Precautions

– Normal diet (carbohydrate 150g/day)

– Absence of diseases which are known to cause hyperglycemia

• Limitations

– Fasting hyperglycemia occurs relatively late in some patients of NIDDM

• Post challenge plasma glucose/OGTT is suggested when fasting glucose is between 5.5-7.8 mmol/l.

• Note: after 50 yrs of age; add 0.6 mmol per decade or 1 mg/year to the diagnostic criteria

Random Plasma Glucose

• In healthy individuals, plasma glucose conc. Vary only slightly throughout the day and generally are in the range of 2.5-7.3 mmol/l. The only rise that occurs is found following a meal.

• Diagnostic value

– > 11.1 mmol/l – dm

– < 2.5 mmol/l hypoglycaemia 7.8-11.1 mmol/l

– Further investigations

• Random glucose has no value in screening, diagnosis and follow up of DM

• It has greatest value in comatosed patients, whether known or preveiously unknown diabetes.

Post Challenge Plasma Glucose

• Glucose load = 75 g

• Plasma glucose conc. Is determined 2 hrs later

• It allows for more objective conditions of testing and a more precise comparison of an individual’s response with a large population. This test is more precise than a postraprandial glucose

• However this test requires more preparation

• Unrestricted activity

• Carbohydrate diet

• Fasting

• Diagnostic value – 11.1 mmol/l

Two Hour Postprandial Plasma Glucose

It has been used to screen for diabetes mell-itus, to diagnose diabetes and to monitor glucose control. The significance of the 2 hrs postprandial value is limited by the lack of rigidly controlled conditions

• Amount of carbohydrate

• Time used to consume meals

• Type of food

• Age of the patient

• Time of the day

These factors are responsible for the differences in the interpretation of the results

• Interpretation:

– Glucose value < 7.8 mmol/l normal

– Glucose value 7.8 – 11.1 mmol/l ogtt

– Glucose value >11.1 mmol/l dm

Sampling For Blood Glucose

A. Whole blood allowed to stand at room temperature shows decrease in glucose from 7-10% in one hour

• The erythrocytes of newborn infants consume glucose more rapidly (20-30%/hrs)

• Procedures for the prevention of glycolysis in blood specimens should be adopted to prevent decrease in glucose before estimation

B. Venous/capillary blood

C. Plasma/whole blood

• It provides more stable values for glucose

• No effect of hematocrit

• It reflects the extracellular glucose concentration more accurately

Conclusions

• Fasting plasma glucose can be offered as a single screening test

• The patients having fasting glucose level between 5.5 – 7.8 mmol/ can be further evaluated with either post challenge glucose or OGTT

• Random glucose should only be reserved for patient presenting as medical emergency

• 1 mg/dl per year of age (0.6 mmol/decade)after the age of 50 years must be added to the accepted normal range of glucose for correct interpretation of the results.

Looking for complications

Need to monitor for long-term complications – biochemistry is useful as a screen

– Renal

• Plasma creatinine (50-140 µmol/l)

• Urine “microalbumin”

• < 30 µg/min in resting overnight sample

– Lipids

• Fasting triglycerides (< 1.7 mmol/l)

• Cholesterol (< 5.1 mmol/l)

– ? Thyroid function tests

• Autoimmune association IDDM

• May be justified especially in elderly females

Acute events

Diabetic Ketoacidosis

• Caused by insulin deficiency and often precipitated by intercurrent illness

• increased glucagon, cortisol, catecholamines, GH causes increased hepatic glycogenolysis & gluconeogenesis and unrestrained FFA release from adipose tissue

• beta-oxidation in liver produces excess ketone bodies causing acidosis

• dehydration due to osmotic diuresis leads to renal impairment and failure to compensate for acidosis

• Usually a long prodromal period followed by a rapid onset of acidosis and catastrophic collapse

DKA – Biochemistry

• Severe Acidaemia & Acidosis

– pH may be 6.75 – 6.9 (ref 7.35 – 7.45)

– Kussmaul breathing

• Hyperglycaemia

• Hyperkalaemia

– H⁺ exchange across membranes for K+

– but note this masks a severe intracellular K+ deficiency

DKA -diagnostic testing

• Clinician – at bedside

– test strip blood glucose

– arterial blood pH, pO₂, pCO₂

• Laboratory

– confirms glucose

– plasma U&E (creatinine unreliable)

• low sodium

– may be due to glucose osmotic dilution

– may be pseudo due to hyperlipidaemia

• high potassium

– due to acidosis

Hypoglycemic Coma

Symptoms : coma, tachycardia, sweating, fits

• Immediately test strip glucose

– beware credibility of low results

– and failure to diagnose

• Treat if in any doubt – glucose is harmless!

• Confirm with lab blood/plasma glucose BUT take sample before treatment

– blood glucose < 2.2 mmol/L

– plasma glucose < 2.5 mmol/L

Hyperosmolar Hyperglycaemic coma (HONK)

• Elderly NIDDM

– some mild ketosis, lack of hyperventilation

– 50% raised plasma Na > 150mmol/L

– glucose typically 50 – 60 mmol/L

• 50% mortality – widespread venous thrombosis

• Good prognosis if well managed

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