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

One of the major aspects of a good diabetic management is that the blood glucose levels should be optimally controlled. Whilst there are a few who may still question the role that hyperglycemia plays in the pathogenesis of the dreaded long term complications, most of the authorities are of the view that an optimal control of the blood glucose level will definitely help in retarding the progression of these complications even if one is not able to completely avoid the problems. By optimally, I would mean that they should be as close to normal as is possible without exposing the patient to the "peaks" of hyperglycemia as well as the "troughs" of hypoglycemia.

But how are we to judge the adequacy, or otherwise, of the control of the glucose levels? What are the parameters available which enable us to get a correct idea of the control?

Unfortunately, many of the so-called parameters which have traditionally been used to judge this control have so many shortcomings associated with them, that they should have no place in the modern management of diabetes. At the same time, one cannot accept all new methods of evaluating blood glucose control without inspecting their feasibility in our context. Having made this point, what are the methods that we commonly use to judge blood glucose control.

Presently, the following methods are in vogue :

1. Testing the urine for the presence of glucose;
2. Occassional blood glucose test done in an laboratory ;
3. Estimation of Glycosylated Hemoglobin and serum Fructosamine levels ;
4. Self monitoring of the blood glucose levels.

URINE TESTING FOR THE PRESENCE OF SUGARS

This is still the most common method used for estimating the blood glucose control ! I feel that using this estimation is in today's context mostly unacceptable, especially when other, better, parameters are easily available. Urine tests are associated with too many shortcomings to give any reasonable answer about the glucose control. At the same time, it would be worthwhile to examine the reason why urine testing for glucose was advocated as a means of evaluating blood glucose control as a time when other methods were not routinely available.

When blood flows through the kidneys, glucose that is present in it is filtered by the glomerulii. When this filtrate flows through the tubules, this glucose is reabsorbed back into the bloodstream and consequently, under normal circumstances, no glucose is found in the urine. The capacity of the tubules to reabsorb glucose is limited and if the amount of filtered glucose is more than this capacity, the excess glucose would be found in the urine, which would then test positive for the presence of glucose. As the amount of glucose found in the glomerular filtrate is dependent on the amount of glucose present in the blood, it follows that in cases where the blood glucose levels are increased, as in diabetes, more than normal amounts of glucose would be filtered out and if this overwhelms the reabsorptive capacity of the tubules, glucose would be found in the urine.

This has lead to the concept of "renal threshold". This is the blood glucose level beyond which so much glucose would be filtered out by the glomerulii that the urine would test positive for the presence for glucose. The textbooks mention the renal threshold for glucose to be 180mg%. In other words, if the blood glucose levels were to increase above 180mg% then the urine would test positive for the presence of glucose.

In view of this, it is easy to understand how testing the urine for the presence of glucose came to be used as a parameter to judge the blood glucose levels in the olden days. In the absence of wide availability to test for the blood glucose levels, it was felt that if the urine showed the presence of glucose, then it could be surmised that the blood glucose were above 180%. This is where the first fallacy creeps in. One must realise that the figure of 180% is just an average approximation and that the threshold differs markedly in every individual patient. Thus, there are those non-diabetics who will show the presence of glucose in their urine, even when the corresponding blood glucose level may be only 100mg% ! Conversely, some known diabetics may not show the presence of glucose in the urine, although their blood glucose levels may have reached as high as 300mg%. Most of the others would come in between these two extremes. Therefore, if urine testing is to have any relevance to judging the blood glucose control, then the renal threshold for every individual patient will have to be charted ! Unfortunately, the method for estimating the renal threshold is quite cumbersome and one should not be under the misconception that it just a simple matter of checking the urine for the presence of glucose and estimating the corresponding blood glucose levels. This "simple" method will invariably give wrong idea of the renal threshold as we shall discuss later.

Even if we were to take the trouble to estimate the renal threshold for every individual patient, we are then faced with the problem that this value does not remain constant for that individual for all times. The threshold value changes with age, pregnancy, any kidney disease including diabetic nephropathy. More importantly, and this is not too well known, changes in the blood glucose level themselves can effect a change in the renal threshold values ! It is now well accepted that when the blood glucose levels are very high, the renal threshold values tend to be lower and this then increases gradually as the blood glucose levels are brought under control. In other words, the very parameter that we use to judge blood glucose control, itself undergoes changes as the blood glucose levels change !

It should be obvious that such a labile renal threshold value should not have any important place to play in judging the blood glucose control in the modern context.

There are many more reasons why we should not use urine glucose tests to evaluate blood glucose control. For the purposes of discussion, let us take a theoretical patient and accept that his renal threshold value for glucose is 180mg%. What this implies is that if the patients blood glucose values are below 180mg%, then no glucose would be found in the urine. Often, we test the urine in the fasting stage and feel gratified that is shows no glucose. But are we justified in accepting that this signifies good control ? It is possible that the blood glucose levels may be 165mg% and this value in the fasting stage would definitely be unacceptably high ! Looking at this from a slightly different angle, when the urine shows the absence of glucose, it would mean that the corresponding blood glucose level could range, in theory, from 0mg% to 180mg%, a complete range from the absurdly low to the unacceptably high. How is it possible to accept such a parameter to judge blood glucose control, leave alone making treatment changes !

Thus, testing the urine for the presence of glucose as an indirect parameter to judge blood glucose control is, at best, a crude method and should be accepted as such.

Even if we are to accept that urine tests are only crude method and give us only a rough idea of the blood glucose levels, we would be erring. It should be realised that urine test for the presence of glucose does NOT give an estimate of the blood glucose levels at the very time of testing the urine. In simple terms, we test the urine for glucose, say, 2 hour after a meal, as patients are often asked to do. Let us for the sake of discussion accept that the renal theshold of the patient is 180mg%, 1 + urine sugar corresponds to 200mg%, a 2 + to 250mg% and so on. The patient tests his urine after two hours of a meal and finds that his urine shows a 2 + presence of sugar in the test. Can this be taken to mean that his blood glucose level 2 hours after the meal is 250mg% ? This could be completely off the mark. In this case, one may accept the blood glucose level at that time to be 250mg%, only if the urine that we are testing is that which is passed by the kidneys precisely 2 hours after the meal. But the urine that we are, in reality, testing is NOT the freshly passed urine but a mix of all the urine that has accumulated in the urinary bladder since the last time that the patient had voided. In other words, urine testing cannot give us a true idea of the blood glucose levels at the time that we test the urine. This point, though of utmost importance, is often forgotten by many of us.

One way out of this problem would be to ask the patient to completely empty his bladder, say, 5 minutes before the test and discard this urine. He would then pass a fresh sample of urine after about 5 minutes and this could then be construed to be akin to a freshly passed specimen from the kidneys and this may give an idea of the corresponding blood glucose levels in an ideal situation. To do this, that is to completely empty the bladder and then pass some more urine within 5-10 minutes is more easily said than done. Most, if no all patients find this extremely difficult (not to say inconvenient) and many will refuse to do the test at all. I always ask doctors who advise their patients to do this, if they have ever tried to do it themselves. Only then they will realise how troublesome these instructions are ! Often, the patients are advised that after they have discarded the first urine completely, they should drink lots of water. This is done in the hope that it will help them offer the second sample easily. Unfortunately, the very fact that the patient drinks a lot of water, makes him pass dilute urine, and this dilution in itself, changes the renal threshold !

More commonly, many diabetics have some amount of autonomic nerve involvement and this leads to an inability to completely empty the urinary bladder. Such patients, and there are quite a few of them, would find it impossible to offer a second, fresh sample of urine, as any urine that they pass would invariable have been mixed with some of the urine that has remained in the bladder due to incomplete emptying caused by the neuropathy. This inability to completely empty the urinary bladder caused by the neuropathy, leads to some urine stagnating in the bladder and this urine is particularly prone to get infected especially in diabetics with a high blood glucose levels who would pass an increased amount of glucose in the urine. The infecting bacteria will utilise the glucose that is present in the urine and when we test the urine, under such circumstances, one would find an absence of sugars. This would lead to a completely erroneous idea that the blood glucose control is quite acceptable. In reality, the blood glucose may be very high but this would not be reflected in the urine tests just at the time when it would be important to correctly assess the diabetic control so that adequate measures can be taken to manage the blood glucose levels and help in the eradication of the urinary tract infection.

Finally, let us briefly discuss the methods that are widely used in many parts of our country. The two most commonly used methods are the older Benedict's test and the "stick" test. The Benedicts test is the older test in which a certain amount of urine is added to a measured quantity of the blue copper sulfate solution, and the mixture is boiled after which the change in colour of the solution and precipitate, if any, is noted. This change in the color is supposed to indicate varying levels of sugars in the urine.

This test is still very widely used here, the main reason being its cheapness. But, it is also very non-specific and will show a positive reaction with many a reducing substance besides glucose. To give a common example, breast feeding mothers excrete lactose in the urine and the Benedicts test will show a positive result even though the blood glucose of the mother are completely normal and she is not spilling any glucose in the urine. There are numerous drugs and medications that also interfere with the correct result as we shall discuss later.

The "stick" has a special paper attached to one end. This paper is impregnated with certain enzymes and when it is dipped into the urine, the change in the color of the paper will denote the presence of, and the varying amounts, of glucose present in the urine. It has the advantage that it is quite specific for glucose and also does not require all the paraphernalia that one needs for the Benedicts test like test tubes, dropper, a source for boiling the solution etc. At the same time, it is costlier than Benedicts test, although the cost can be halved by cutting the strip longitudinally so that one can use each stick twice.

It, too, has drawbacks, the chief one being that there are many drugs and medications which interfere with the correct result. These drugs may interfere with false positive or false negative results. Just to show how common the problem can be, two rountinely used drugs which can interfere with the results are aspirin and Vitamin C. Thus, doing urine tests for the presence of sugar when the patient is on any of these tablets would give a completely wrong result. These drugs are so commonly used even by patients themselves that doctors are often unaware that the patient is on these medications. I do not think that it would be possible to find a single diabetic patient who is not taking a vitamin tablet and aspirin is a common household remedy for aches and pains and also now routinely prescribed as a preventive measure against atherosclerosis.

Does this imply that testing the urine for the presence of sugars has no role to play in the modern management of diabetes? Whilst, it would seem to be so, especially when other better methods are now available to judge blood glucose control, it should also be remembered that many of these methods are not easily accessible or affordable to many of our patients. They also have their inherent drawbacks. Therefore, I feel, that in spite of all the problems associated with the use of this mode of testing, it will continue to be used by many patients. One of the main reasons is the relative cheapness of the method, but more importantly, due to the fact that most of the patients are unaware of the useless results that one can get from such tests.

Urine testing will continue to be important to look for the presence of ketones and albumin in so far as diabetes management is concerned as well as to rule out mild, asymptomatic, urinary tract infection. Some authorities feel that urine testing for glucose may be an adequate parameter to judge blood glucose control in the elderly diabetic who does not have any other complication. The reasoning behind this is that elderly diabetics tend to have a higher threshold and are also quite averse to having the blood tested frequently. Under such circumstances, if the urine shows the presence of glucose, then it could be surmised that the blood glucose levels must be quite high and need to be brought down. Conversely, many young diabetics have a low threshold and a consistent absence of glucose from their urine should be a pointer to the possibility that they many be undergoing subclinical hypoglycemia. Frankly, I am not convinced about either of these aspects. From a practical compromise view point, a newly diagnosed patient with a blood glucose of 400mg% and a urine glucose of 4+, may be monitored by testing the urine glucose till it comes down slightly, to say 2+, and then one must shift to monitoring the blood glucose levels.

Finally, if one is going to utilise these tests to evaluate diabetes control it would be better to use the "stick" method, as this is somewhat specific for glucose. At the same time, it is essential that one be aware of the pitfalls associated with these urine tests so that one is not lulled into a false sense of complacency about the glycemic control when the tests for the presence of sugars in the urine are negative. Conversely, drastic changes in the treatment schedule should be avoided just on the basis of urine test results

Urine testing, is at best, a very crude method for evaluating blood glucose control and should be accepted as such.