Diabetes mellitus is a multifactorial disease caused by deficiency or ineffectiveness of a Insulin, a protein secreted by pancreas. Insulin is sensor of blood glucose level. It effectively keeps blood glucose level (BGL) within a narrow range of 60-90 mg/dl. This is important because when blood glucose crosses this limit, there are serious consequences.
- If blood glucose falls (below 60 mg/dl), the condition is called It is a serious condition as it may cause loss of consciousness, coma and death.
- If blood glucose rises abnormally, the condition is called Prolonged hyperglycaemia may cause damage to a wide range of body organs and tissues, including heart, kidneys, eye lens, retinal and nerves. This may result in heart attack, kidney failure or blindness.
Two major types of diabetes are known: type 1 and type 2. Of these, the type 1 is more serious. It occurs in younger age group (below age of 20) and the patient requires daily insulin injections for survival. The insulin therapy must continue for entire life. Type 2 diabetes is disease of middle-aged and older individuals. It is more prevalent but less severe: it can be managed by oral drugs, exercise and dietary restrictions only. American Diabetes Association (ADA) has recommended guidelines for screening of diabetes (see Box 1).
Hyperglycaemia (abnormally elevated BGL) is the biochemical hallmark of diabetes, but various other metabolic indices are also deranged. These form biochemical basis of diagnosis and monitoring of diabetes, and for early detection of diabetic complications. Various tests for aforementioned purpose are discussed in this article.
Tests for diagnosis of diabetes:
- Uriane analysis is a quick screening test. Glucose starts appearing in the urine whenever blood glucose exceeds 180 mg/dl. The condition is called Earlier a test called Benedict test was used for detecting glucosuria. Now a days dip stick methods are available, where glucose can be detected by dipping paper-strips in urine sample.
Urine is also analyzed for ketone bodies. These are abnormal compounds, produced in patients having poor control of diabetes. Again dip-stick methods are available for their detection.
- Determination of fasting blood glucose (FBG) level is the most important laboratory test for diabetes. Blood sample is collected after an overnight fast. The FBG should not cross 100 mg/dl. Diagnosis of diabetes is confirmed, it the FBG crosses 126 mg/dl on two different occasions. Thus, 126 is the diagnostic cut-off presently though this is subject to further modifications lately.
Borderline cases, called prediabetes, need special mention: FBG between 100-125 is considered prediabetes. Such persons are at risk of developing diabetes in future.
- Oral glucose tolerance test (OGTT) is a reliable test for diagnosing and evaluating borderline diabetes. OGTT involves measurement of blood glucose both immediately before and at defined interval (2 hours) after ingestion of a glucose solution.
The patient is asked to fast overnight and blood glucose is measured. (S)he is then given a sugary liquid (75 gm glucose in 300 mal water) and blood glucose is measured after 2 hours. In normal individuals the blood glucose returns to fasting level within 2 hours. Diagnostic cut-off here is 200 mg/dl, meaning that blood glucose rises above 200 mg/dl in diabetes.
(Note: If the 2-hour BGL is between 140-200, it is a case of prediabetes)
- Tests for monitoring of diabetes: Blood glucose, estimated periodically, remains the mainstay for monitoring of diabetes. It should remain within the limits mentioned above.
Haemoglobin A1c is measured to assess monitoring. This product is formed by nonenzymatic glycosylation of haemoglobin, as explained below
Haemoglobin is a transport protein present in our blood. It serves to carry various substances, including two gases: oxygen and carbon dioxide. Glucose present in blood can attach with Hb; the process is termed glycosylation. Product of glycosylation is called glycosylated haemoglobin; abbreviated as HbA1c. The concentration of HbA1c is proportional to the blood glucose level:
- In normal persons it is 4-6%
- In diabetic individuals it is 6.5% or above. Poorer the diabetic control, higher the value.
Target values of less than 7.0% are recommended for diabetic persons. Because haemoglobin has life-span of 4 months, this test provides information about the average severity of hyperglycamia during the last few weeks (4-6) before the test.
- Tests for detecting diabetic complications: As mentioned earlier, several complications may arise in long term diabetes due to damage to tissues/organs. Biochemical investigations play important role in detecting these at an early stage.
Tests for detecting renal damage: Long term diabetes, if uncontrolled, can damage kidneys. The condition is called diabetic nephropathy. Following tests are used to detect it:
- Microalbuminuria: The damaged kidney leaks a small amount of albumin (a blood-protein) into urine. Leakage less than 30 mg in 24 hours is observed in normal persons. Excretion of 30 to 300 mg indicates is termed microalbuminuria. It indicates early kidney damage
- Macroalbuminuria: Excretion of more than 300 mg/24 hours is termed macroalbuminuria. It indicates a more advanced kidney damage.
The first step in the screening and diagnosis of diabetic nephropathy is to measure albumin in a spot urine sample, collected either as the first urine in the morning or at random, for example, at the medical visit. This method is accurate, easy to perform, and recommended by American Diabetes Association guidelines.
The results of albumin measurements in spot collections may be expressed as urinary albumin concentration (mg/l) or as urinary albumin- to-creatinine ratio (mg/g or mg/mmol). Although expressing the results as albumin concentration might be influenced by dilution/concentration of the urine sample, this option is still accurate and cheaper than expression as albumin-to-creatinine ratio.
These tests should not be performed in the presence of conditions that increase urinary albumin excretion (UAE), such as urinary tract infection, hematuria, acute febrile illness, vigorous exercise, short-term pronounced hyperglycemia, uncontrolled hypertension, and heart failure. Samples must be refrigerated if they are to be used the same day or the next day, and one freeze is acceptable before measurements.
- Test for evaluating risk to heart: Periodic estimation of lipid profile is a reliable method for assessing risk to heart. The parameters commonly estimated and their normal levels are as below:
Lipid parameter (blood) Concentration
Triglyceride <150 mg/dl
Total cholesterol <200 mg/dl
LDL cholesterol <100 mg/dl
HDL cholesterol 35-59 mg/dl
Rise in these parameters (except HDL cholesterol) indicates poor outcome for heart. Rise is HDL, on the contrary, indicates good for heart. These parameters should be periodically estimated in all diabetic individuals.
Finally, considering the fact that prevalence of diabetes is increasing, it is desirable that screening should be carried out vigorously. Early diagnosis will help, as evident from the above discussion. The American Diabetic Association recommends that the following people be screened for diabetes:
- Anyone with a body mass index higher than 25 (23 for Asian Americans), regardless of age,who has additional risk factors, such as high blood pressure, abnormal cholesterol levels, a sedentary lifestyle, a history of polycystic ovary syndrome or heart disease, and who has a close relative with diabetes.
- Anyone older than age 45 is advised to receive an initial blood sugar screening, and then, if the results are normal, to be screened every three years thereafter.
- Women who have had gestational diabetes are advised to be screened for diabetes every three years.
- A person who has been diagnosed with prediabetes is advised to be tested every year.
As the biochemical tests are getting within reach of general population, it is expected to improve quality of life and avert complications.
- By Dr Parul Gupta & Dr Preeti