Dr. S.M.Sadikot.
Hon. Endocrinologist,
Jaslok Hospital and Research Centre,
Mumbai 400026

The prevalence of diabetes is increasing quite rapidly in our country. In fact, most people now feel that we should consider this as an "epidemic"!

Whilst a significant part of this increase can be attributed to changes in life styles and eating habits, a large part of the increase is due to the health consciousness amongst the people who are keen to get investigated. There is such an increased awareness about diabetes amongst the general population and many are aware that if diabetes is detected at an early stage and steps taken to optimally manage it, one can hope to escape from the dreaded ravages associated with diabetes especially in their severe and debilitating form.

The converse is also true. Inspite of the increased awareness recent studies have shown that for every person known to have diabetes, there are more than 2 people who have diabetes but are unaware of it.

Although diabetes does have its typical signs and symptoms, many people do not exhibit these "typical" signs and symptoms even though they have diabetes.

In fact, many persons with Type 2 diabetes already show the presence of the long term complications associated with diabetes at the time of diagnosis. Thus, this is all the more reason to try and diagnose the onset of diabetes at the earliest.

Unfortunately, unless the method of testing is correct and the data interpreted accurately, one can end up with quite erroneous results as these case reports illustrate.

Mr. A.S., a male aged 72 years was referred to the hospital with weakness, unsteady gait, giddiness and "diabetes". He had been found to be diabetic about 2-3 weeks previously when his 2 hour postmeal glucose had been found to be 171mg% (normal for the laboratory: 130mg%). He had been given a diabetic diet and prescribed some tablets for his diabetes. When his random blood glucose was examined, it was seen to be 38mg%! Going into some detail, it was found that the blood had originally been estimated by the Folin-Wu method. This is an extremely outdated method and measures all the reducing substances present in the blood and may overestimate the true blood glucose levels as much as 20-30 mg%.

Moreover, the patient had also been prescribed steroids for bronchial asthma at the time of his original test and these drugs are well known to increase the blood glucose levels. Due to these factors, and also in view of the age of the patient (older patients do tend to have some increase in their blood glucose levels), the oral hypoglycemic agents were discontinued and the patient given a normal diet. With this, the patient made an excellent recovery and has been followed up now for about 2 years and continues to keep in good health with his subsequent tests for diabetes all being within acceptable limits. Here was a patient who was not a diabetic but incorrect testing and a wrong interpretation of the results had led to an erroneous diagnosis. Fortunately, the patient could recover before there was any serious or permanent damage.

Mr. F.G., a male aged 36 years had repeated attacks of cough, cold, fever and weight loss. On investigation, he was found to have pulmonary T.B. Inspite of being put on the correct anti-T.B. medications, the patient did not feel any better and in fact, his condition seemed to worsen. Due to the fact that both his parents had diabetes, his urine was tested for the presence of sugars and when this showed a negative result, diabetes was ruled out. When his condition deteriorated further, he was admitted to the hospital.

Here, an estimation of a fasting blood glucose levels showed the levels to be 368mg%! His urine did show the presence of acetone, but no sugar. With a good management of his blood glucose levels and continued treatment for T.B., the condition of the patient improved and he is doing fine at present. He just happened to one of those persons who have a high renal threshold! It is quite plausible that if he had been correctly tested for diabetes at an early stage, he may not have worsened enough to warrant an admission to the hospital. In other words, unless the test is done correctly and the data are accurately interpreted, one could end up with quite "catastrophic" results.

Before, we discuss the correct and accepted method to diagnose diabetes, I would like to discuss one other aspect. I am often asked as to who should get themselves tested for diabetes.

All those who complain of symptoms or show signs commonly associated with diabetes must have a test for diabetes, if feasible, all persons over the age of 30 years should undergo an annual test to rule out the presence of diabetes.

A negative test for diabetes does NOT mean that the person will never get diabetes. It only means that the person does not have diabetes at the time of testing.

Persons at high risk MUST undergo testing when they present for medical attention for whatever reason, and if negative, must have a regular check, thereafter.

• All persons manifesting any of the following signs and symptoms: polyuria, polydipsia, polyphagia, weight loss inspite of adequate food intake, undue tiredness and fatigue, tingling or numbness in the extremities, burning feet, generalised pruritus, pruritus vulvae, balanitis,delayed wound healing, impotency, premature cataracts, visual disturbances. Although diabetes has many and varied signs and symptoms, these, in my opinion are the commonest in people with diabetes.
• All persons with a family history of diabetes.
• All obese patients, especially those with central obesity, waist-hip (W-H) ratio, approx. >0.95 in men and >0.85 in women, and/or a Body Mass Index (BMI) >25.
• All adult patients with tuberculosis, including atypical presentations, recurrent infections, non-healing ulcers.
• Patients with atherosclerosis and its complications, especially those with premature acrovascular disease.
• All patients with high blood pressure and lipid abnormalities.
• All women with a bad obstetric history, recurrent fetal wastage, and those who give birth to large weight babies.
• Persons who were large weight babies; very low birth weight babies may also be predisposed to diabetes.
• Persons who show an acute rise in the blood glucose levels at time of physical (myocardial infarction, cerebrovascular accidents, acute infections, trauma, etc.) or mental stress.
• Persons taking drugs which are known to increase blood glucose levels like steroids, thiazide diuretics, oral contraceptives, beta-blockers, phenytoin sodium, etc.

Ideally,
All persons over the age of 30 years should undergo an annual test for the presence of diabetes

First and foremost, urine examination for the presence of sugars should NEVER be the method to diagnose diabetes. This cannot give results of any value.

The diagnosis of diabetes can only be done by estimating the true blood glucose levels and interpreting the results according to widely accepted criteria. The method by which the blood is analysed for glucose is also of importance. The Folin-Wu method is too outdated for use. Even the Somogyi-Nelson and the Hoffman methods should not be utilised. The only presently accepted way of analysing blood for glucose is to use to Glucose Oxidase method, and the laboratory to which the patient goes for the diagnosis should be one which routinely uses this analytical method. It is also important to note whether the laboratory, even though using the glucose oxidase method, uses capillary blood, whole venous blood, or venous plasma for the estimation. The levels of glucose in plasma are about 15% higher than the levels in whole blood and the diagnostic criteria differ. Unless one is aware of the material used in the analysis, one will not be able to accurately interpret the results.

Unfortunately, most of the laboratories even though they may mention the method used, do not say which material (whole blood or plasma) has been utilised. Therefore, one would have to make it a point to find out from the laboratory about this aspect.

In the occasional patient, especially those manifesting some of the characteristic signs and symptoms of diabetes, one may be able to diagnose diabetes based on the result of a single sample of blood. This could be in the fasting stage, one or two hours after food or even with a random blood sample. If the values obtained are higher than those generally accepted to be in the diabetic range, then one may not need to test the patient after stressing him with glucose.

A fasting venous whole blood glucose of more than 110 mg% (venous plasma glucose > 126 mg%) OR a random venous whole blood glucose level of more than 180 mg%, (venous plasma glucose > 200 mg%), confirmed on repeat testing, in a patient with characteristic sign and symptoms of diabetes, is diagnostic.

The American Diabetes Association (ADA) has recommended that it is no longer necessary to do a fill Glucose Tolerance Test (GTT) in order to diagnose diabetes and that a fasting sample is adequate to make the diagnosis. More importantly, the blood glucose levels at which a diagnosis is made have been significantly changed and it becomes essential for everyone to note these changes as the new values have even been accepted by the World Health Organization (WHO) although the latter has not totally given up the concept of doing a GTT.

Before, we discuss the criteria, a few words on the manner of carrying out a GTT as it continues to be widely used.

Procedure

• The person to be tested must be on their usual diet, exercise and routine schedule for at least 3 days prior to the test. The patient undergoing the test should be on his normal diet for atleast 3-4 days prior to the test. It is felt that the person should be taking around 300gms. of carbohydrates daily during these days. This should not be a problem in our patients as most indian diets do contain this amount of carbohydrates. It is essential that the patient be told about this need for taking a normal diet for a few days prior to the test. Many people starve themselves before the test. They are so afraid of being diagnosed as a diabetic that they feel that by not eating properly for a few days before the test, the blood glucose levels will decrease and they will be found to be non-diabetic. It is obvious that this should never be done. Firstly, starving oneself before the test usually results in an abnormal result. Secondly, and more important., the very idea of doing the test is to correctly diagnose diabetes so that if it be present, then adequate measures can be taken to optimally control it. It is better not to test than to try and vitiate the results!
• The test should be carried out in the morning after fasting for 8 hours; blood is collected in the fasting state.
• The patient must be instructed to go for the test after 8-10 hours of fasting. In my opinion, some amount of water can be taken as there is no adequate proof that this would interfere with the test. After the blood is collected in the fasting stage, glucose will be give to the patient. It may be mixed with as much water as is necessary so that the mixture is not so sweet that it causes nausea and the, patient vomits. A dash of lemon may be added to make the drink more palatable. The glucose solution should be ingested within 4-5 minutes.
• The amount of glucose used is 75 gms of anhydrous glucose (for children the dose is 1.75 gms of glucose per kg of body weight upto a maximum of 75 gms). If glucose monohydrate ( which is the form of glucose most commonly available in the market) is used, 82.5 gms. must be administered.
• The person must rest throughout the test. After the glucose is taken, the patient must remain seated for the duration of the two hours when the second sample will be collected. This should be made very clear to the patient when he is sent for the test. Often, the patient takes the glucose and then goes out, does some work and then returns in time for the second sample. This is not correct if one is aiming for an accurate result.
• Smoking should not be permitted during the test.
• Whilst interpreting the test results, one must know whether the patient is taking any medications as many drugs are known to affect the blood glucose levels. I also ask the patients if they are suffering from any illness or did so in the near past and their level of activity. The age of the patient may not be relevant to the diagnosis of diabetes but would definitely be needed whilst planning any treatment.
• Blood is collected 2 hours after glucose ingestion.
• The results are interpreted according to the W.H.O. criteria.

When analyzing the results, it becomes apparent that all the test results can be divided into three main categories: people who have diabetes, people who do not have diabetes and an intermediate category which depending on the method of testing is known as having either Impaired Glucose Tolerance (IGT) or Impaired Fasting Glycemia (IFG).

Before the ADA changed the procedures for testing, one had to carry out the full 2 hours GTT. When the results of this are analysed, one could be diagnosed as having IGT. This is an intermediate category between those who have frank diabetes and those whose results fall clearly in the normal range. Some of these patients will later go on to have diabetes, whilst others may not progress to the stage of frank diabetes. Patients falling in this category should be closely followed such that, if they progress to the diabetic stage, this would be diagnosed at an early stage. At the same time, many of the patients who are in the IGT category tend to be overweight, have problems with their lipid levels, are hypertensive and have a higher than acceptable serum uric acid level. I.G.T. is risk factor for the development of macrovascular disease.

Thus even if these patients are not diabetics, they should undergo management for these problems.

If one uses only the fasting values as suggested by the ADA, it would not be possible to diagnose IGT as the 2 hours postglucose values needed for a diagnosis of IGT would not be available. Impaired Fasting Glycemia (IFG) is an entity which has recently been introduced to delineate persons in whom only the fasting blood glucose has been done, but who do not come in the normal or diabetic category. Many of the associated disorders we mentioned as being possibly present in those with IGT are also true for those with IFG. In fact, IFG is felt to reflect a higher average glycemic burden than IGT. It is considered a marker for the development of diabetes and its long term complications.

Although there is still some controversy about using only the fasting blood glucose values for diagnosis, it is now felt that this would be acceptable to pinpoint those with diabetes in prevalence studies. The WHO feels that in most cases this should be followed by a full GTT, if feasible.

Most people tested would show "normal" values.

But, "A NEGATIVE TEST RESULT ONLY SHOWS THAT THE PERSON DOES NOT HAVE DIABETES AT THE TIME OF TESTING. IT DOES NOT MEAN THAT THE PERSON WILL NEVER GET DIABETES IN THE FUTURE. WHICH IS WHY AN ANNUAL CHECKUP IS ESSENTIAL".

Gestational Diabetes Mellitus (GDM) is defined by abnormal glucose tolerance during pregnancy; the glucose tolerance test is normal before, and which will usually be normal, after pregnancy. Present in around 3-4% of all pregnancies, GDM can be associated with significant morbidity and mortality in the fetus and newborn. Thus, it is important for gestational diabetes to be ruled out in all pregnancies.

Ideally, all pregnant women should be tested to rule out gestational diabetes, but if this is not feasible, all high risk patients must undergo the test.

1. Women who had GDM during a previous pregnancy.
2. Women with a first degree relative who is a diabetic.
3. Women who gave birth to large weight babies in a previous pregnancy.
4. Women whose newborn, in a previous pregnancy, showed any complication known to be associated as arising from maternal GDM.
5. Women who gave birth to still born babies or infants with congenital abnormalities.
6. Women with a bad obstetric history, including recurrent fetal wastage, hypertension, eclampsia, hydramnios, etc.
7. Women with repeated or persistent urinary tract infection.
8. Women manifesting glycosuria during pregnancy.
9. Women over the age of 30 years.

The test should be carried out at the time of initial visit and at the start of every trimester; high risk patients may require more frequent testing.

Initial screening produce may be done by estimating the fasting glucose levels and the levels 1 hour after an oral dose of 50 gms. of glucose. This test can be carried out in the fasting stage or at any time; in the latter case, only the one hour blood glucose value is taken into consideration for diagnosis.

Patients with a fasting venous whole blood glucose level of more than 80 mg% (venous plasma glucose more than 90 mg%).

OR

a 1 hour post 50 gms. glucose load venous whole blood glucose value greater than 120 mg/% (venous plasma glucose more than 140 mg% require a more comprehensive test.

OR

A "random" venous blood glucose level exceeding 105 mg% (plasma glucose >120 mg%) also merits a more comprehensive test.

The comprehensive test is the same as described for the diagnosis of diabetes in non pregnant persons. BUT, the criteria differ. In addition to blood glucose levels in the diabetic range, values suggestive of IGT, in a pregnant female, should be taken to be diagnostic of gestational diabetes.

Many centres still utilise the O'Sullivan Criteria.

In this test, blood is collected in the fasting stage and then at 1, 2 and 3 hours intervals after an oral load of 100 gms. of glucose.

Two of the four values must be met to diagnose GDM.

As a matter of interest, about 30-40% of women who are diagnosed as having gestational diabetes will later go on to have full fledged diabetes within 5-10 years of the pregnancy. Thus, they would automatically come into the High Risk category and must have annual check ups as discussed above.

I am often asked whether an estimation of Glycosylated Hemoglobin level can be used as the parameter to diagnose diabetes. Let me make it quite clear that, at the present times it is not possible to accurately make this distinction between those that are normal and those that have diabetes or may be in the IGT or IFG category. Although the estimation of these levels are excellent to give an idea of the overall control of the blood glucose levels in the preceeding 6-8 weeks, they CANNOT be used for the diagnosis of diabetes, in most patients. The argument that a very high glycosylated hemoglobin level would be diagnostic for diabetes can be very easilv countered by the fact that if the glycosylated hemoglobin level were indeed to be so high, then it is apparent that even a random estimate of the blood glucose levels would show it to be in the distinctly "diabetic" range, and this can be done at much less cost to the patient!

Lastly, once a patient has been diagnosed as being a diabetic, he need NEVER undergo a Glucose Test. This test is only for diagnosis. A known diabetic needs to know whether he is under optimal control or not and stressing him with a glucose load will definitely not give an answer to this problem. This is an important aspect as many doctors, including "specialists", have the patient undergo repeated G.T.T's! When a diabetic comes for a follow up with a fresh G.T.T., it is of absolutely no help in his management.