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